Text

Advisory Committee on the Medical Uses of Isotopes (ACMUI) March 11, 2020 Meeting Ebinder
	ML20056E123
Person / Time
Issue date:	03/11/2020
From:	; Advisory Committee on the Medical Uses of Isotopes
To:	;
	Jamerson, Kellee NMSS/MSST
References
	Download: ML20056E123 (42)
	v • d • e

Advisory Committee on the Medical Uses of Isotopes (ACMUI)

Public Teleconference Meeting March 11, 2020 Meeting Handout

U.S. Nuclear Regulatory Commission (NRC)

Advisory Committee on the Medical Use of Isotopes (ACMUI)

Subcommittee Review and Comments on Draft Final Proposed Regulatory Guide 8.39, Release of Patients Administered Radioactive Materials, Revision 1 (Phase 1) Issue Date: December 2019 Draft Report Submitted: February 24, 2020 Subcommittee Members:

Mr. Gary Bloom Dr. Vasken Dilsizian Ms. Melissa Martin Dr. A. Robert Schleipman Mr. Michael Sheetz (Chair)

Ms. Megan Shober NRC Staff Resource: Dr. Said Daibes-Figueroa Charge During the September 20-21, 2018 ACMUI Meeting, ACMUI Chairman, Dr. Christopher Palestro, established a subcommittee to review the NRC staffs draft proposed revision to Regulatory Guide (RG) 8.39, Release of Patients Administered Radioactive Materials.

Background

The NRCs current RG 8.39, Revision 0, was issued in April 1997, following the rule change in 10 CFR 35.75 to allow the release of patients administered radioactive material on a solely dose-based criteria. Since that time, there have been several challenges to the appropriateness of the release criteria and the associated precautions that are required to be provided to minimize radiation exposure to other individuals from the released patient. Over the past several years, the NRC staff has conducted an extensive evaluation, which included a review of published literature, and stakeholder engagement with licensees, patients, and Agreement States, to determine whether significant regulatory changes to the patient release program are warranted. A summary of this evaluation can be found in SECY-18-0015 Staff Evaluation of the U.S. Nuclear Regulatory Commissions Program Regulation Patient Release After Radioisotope Therapy.1 One of the recommendations was that the guidance in RG 8.39 should be updated, simplified, and made more clear and explicit.

RG 8.39 is currently being revised in two phases. Phase 1 revision of RG 8.39, updates the patient release guidance, including information for patient instructions and updates to Table 3, Activities of Radiopharmaceuticals that Require Instructions and Records When Administered to Patients who are Breast-Feeding an Infant or Child. An initial proposed Revision 1 (Phase 1) to RG 8.39 was 1 of 8

issued in March 2019 and was reviewed by this ACMUI subcommittee, for which the comments and recommendations can be found in our previous subcommittee report.2 The following Subcommittee comments and recommendations only pertain to the Final Draft Phase 1 revision, issued December 2019. In Phase 2 revision to RG 8.39, the dosimetric equations, methodologies, and tables used to calculate dose to members of the public from released patients will be updated.

This Subcommittee will review those changes once they have been published.

Changes and Recommendations to Regulatory Guidance Considered by the Subcommittee General Comment:

The Subcommittee commends the NRC efforts in updating the guidance to licensees on meeting the patient release criteria. The Subcommittee also acknowledges and appreciates that most of the recommendations from its previous report on the initial Phase 1 Revision of RG 8.39 have been incorporated, and we provide for your consideration, our specific comments and recommendations on this final draft Phase 1 Revision.

Summary of Recommendations

1. In the Patient Precautions and Instructions Sections, it should be emphasized that the major source of radiation dose to other individuals will be from external exposure from the patient.

Therefore, the most important precautions to take are measures to reduce or avoid the external radiation exposure from the patient, especially in the early time period after administration of the radionuclide therapy. While the release instructions may also include measures to limit the transfer of radioactive contamination to others, they should not overshadow or detract from the external precautions, as the radiation doses from internal exposure have been demonstrated to be small or negligible.3

2. The patient instructions should be simple, clear, and concise. Consideration should be given to providing instructions at an 8th grade level of understanding, and given in the patients native or primary language. Studies have shown that the primary factor for limiting radiation exposure to others is in influencing the patients behavior.3 As the IAEA noted4, The success of a patient release program is critically dependent on the quality and specificity of the information provided to the patient, the skill with which it is communicated, and whether or not the patient believes the information provided.

3. Discussions on the radionuclide therapy procedure and release instructions should also include a caregiver or family member, if possible.

4. Instructions should also be provided on how long the precautions should be followed. As a guideline, the licensee may consider using several (3-5) effective half-lives of the radionuclide therapy.

5. The Regulatory Guide should not include instructions that are excessive, likely to cause patient anxiety, and not likely to reduce public exposures, such as:

a. Shower 2-3 times a day for the first two days.

2 of 8

b. Try to empty your bladder at least every hour for the first 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months . Empty bladder at least once during the first night.

c. After five days of use, replace the tooth brush. The old one is to be placed with the trash being held for a month prior to disposal.

d. Use a second rinse cycle when washing linen, personal clothing, and towels.

e. Instruction to Drink plenty of liquids should be deleted as it may conflict with the patients medical condition. Excessive fluid intake has been reported to cause hyponatremia, which can cause seizures, coma, and even death.

6. Tables 1, 2, and A1 should be updated to include the new and potential radionuclides used in medicine listed below.

Radionuclide Half-Life Exposure Rate Constant (days) (R/mCi-hr at 1 cm)5 Ac-225 10 0.126 At-211 0.3 0.214 Cs-131 (implant) 9.7 0.679 Cu-67 2.58 0.574 F-18 0.076 5.68 Ga-68 0.047 5.43 I-124 4.2 6.59 Lu-177 6.7 0.181 Ra-223 11.4 0.77 Re-186 3.7 0.103 Re-188 0.71 0.316 Sm-153 1.93 0.481 Z-89 3.27 6.59

7. In Table 3. Activities of Radiopharmaceuticals That Require Instructions and Records When Administered to Patients Who Are Breastfeeding an Infant or Child, the subcommittee supports the guidance for a standardized interruption time period of 24 hours2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months for all Tc-99m radionuclides, and the recommended interruption period to limit the dose to the nursing infant to 1 mSv, and not the regulatory limit of 5 mSv.

8. In Phase 2 revision to RG 8.39, where the dosimetric equations, methodologies, and tables used to calculate dose to members of the public from released patients will be updated, the following issues should be considered:

a. An occupancy factor of 0.75 to 1.0 is unrealistic and cannot be justified for routine application, even for radionuclides with a physical half-life less than one day. Dose calculations should be based on realistic assumptions, and not overly-cautious worst case scenarios.

b. The dosimetric models and calculations must consider an option that uses the effective half-life and/or other patient specific factors for the radionuclide therapy.

c. A dose based model should be developed to provide guidance on when precautions or restrictions would be appropriate following the death of a patient administered a therapeutic quantity of radioactive material.

3 of 8

Specific Comments:

Pg 1, Under Purpose, last sentence: Add the words activities and before dose rates that, and replace the word should with may.

Pg 2, Under Applicable Regulations, Delete the 4th bullet item (including sub bullets) and replace with:

10 CFR 35.75(c) requires 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 total effective dose equivalent is calculated by (1) using the retained activity rather than the activity administered, (2) using an occupancy factor less than 0.25 at 1 meter, (3) using the biological or effective half-life, or (4) considering the shielding by tissue.

10 CFR 35.75(d) requires the licensee to maintain a record for 3 years after the date of release that it provided instructions to a breastfeeding woman if the radiation dose to the infant or child from continued breastfeeding could result in a total effective dose equivalent that exceeds 5 mSv (0.5 rem)

Pg 5, Under Background, 1st paragraph, 3rd sentence: Delete the words a dose limit of 1 millisievert (mSv) (0.1 rem), or.

Pg 7, Harmonization with International Standards: While this newly added section is an appropriate reference to the IAEA work and Report No. 63 Release of Patients After Radionuclide Therapy, the subcommittee questions the use of the term Harmonization as the US patient release criteria is significantly different from the European release criteria.

Pg 8, Section 1.1 Release of Patients Based on the Administered Activity: Suggest moving the sentence The total effective dose equivalent is approximately equal to external dose because the portion of the internal dose that contributes to the total external dose exposure is small or negligible (see Appendix B, Section B-3) to after item d for better clarity.

Pg 9, Section 1.1 Release of Patients Based on the Administered Activity, last paragraph: Delete and 2.3, as it does not pertain to breastfeeding infants or children.

Pg 9, Section 1.1 Release of Patients Based on the Administered Activity: Delete last sentence If a record is required, the licensee may demonstrate compliance by using the records of dosage described in 35.40, Written directives, which references 10 CFR 35.2040, Records of written directives, and 35.2063, Records of dosages of unsealed byproduct material for medical use.

These dosage records are different from the record of patient instruction required by 35.75(d).

Pg 9, Table 1. Activities and Dose Rates for Authorizing Patient Release: This table should be updated to include the new and potential radionuclides used in medicine.

Pg 10, Section 2.1 Activities and Dose Rates That Require Instructions, last sentence: Add or Appendix B after using Equation 2 or 3, and before as appropriate.

4 of 8

Pg 11, Table 2. Activities and Dose Rates above Which Instructions Should be Given When Authorizing Patient Release: This table should be updated to include the new and potential radionuclides used in medicine.

Pg 12, Table 3. Activities of Radiopharmaceuticals That Require Instructions and Records When Administered to Patients Who Are Breastfeeding an Infant or Child: The subcommittee supports the guidance for a standardized interruption time period of 24 hours2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months for all Tc-99m radionuclides, and the recommended interruption period to limit the dose to the nursing infant to 1 mSv, and not the regulatory limit of 5 mSv.

Pg 13, Table 3. Activities of Radiopharmaceuticals That Require Instructions and Records When Administered to Patients Who Are Breastfeeding an Infant or Child, footnote b: Change the word limit to constraint.

Pg 14, Section 2.3 Content of Instructions, 2nd paragraph: Add currently after I-131 is.

Pg 14, Section 2.3 Content of Instructions, 2nd paragraph: Change the last sentence The instructions should include the name of a knowledgeable person and his or her telephone number to contact if the patient has any questions. to read, The instructions should include a telephone number for the patient to contact with any questions. Health care facilities establish an on-call number for emergent or after hours coverage. This may not be the same person responding to such a call every day.

Pg 14, Section 2.3.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals, 1st sentence: Add and caregiver or family member after Engaging the patient and add or family member after familiarize the patient and caregiver Pg 14, Section 2.3.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals:

Change Item a. to read What type of post treatment lodging (e.g., single family home, group home, apartment, nursing home, hotel, detention facility) will the patient use? The use of hotels should be discouraged, if possible.

Pg 14, Section 2.3.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals:

Change Item b. (1) to read Will the patient use a private vehicle, taxi service, ride-booking service, or public transportation (i.e., bus, train, or airplane)? The use of public transportation should be discouraged.

Pg 15, Section 2.3.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals:

Change Item f. to read Can the patient take care of himself or herself, is he or she capable of complying with the release instructions., and create a new item to read Can the patient sleep alone in a separate bedroom or area?

Pg 15, Section 2.3.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals:

Delete Item i. as this is already addressed in Item h.

5 of 8

Pg 15, Section 2.3.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals:

Delete Item j. as this question does not help in determining appropriate patient instructions.

Pg 15, Section 2.3.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals:

Change Item k. to read Can the patient delay returning to work? What kind of work does the person do? For example, is the person a day care provider with significant exposure to young children?

Pg 15, Section 2.3.2 Patient Precautions: Delete the wording in Item a. and replace with The greatest radiation dose potential to other individuals 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 from the patient, especially in the early time period after administration of the radiopharmaceutical therapy.

Pg 16, Section 2.3.2 Patient Precautions: After Item a. (1), add the following two precautions to minimize external exposures:

(2) If the patient is traveling with other individuals to the post treatment lodging location, emphasis should be made to minimize the number of traveling companions and to maximize the distance from the patient.

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

Pg 16, Section 2.3.2 Patient Precautions: After Item a. (3), add a new Item b. to address the precautions to limit the spread of radioactive contamination and minimize internal exposures:

b. The release instructions may include measures that are necessary to limit the transfer of radioactive contamination to others. The licensee should provide specific information 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 how to minimize, isolate, and clean radioactive contamination is important in minimizing exposure to others.

Pg 16, Section 2.3.2 Patient Precautions: After new Item b., list the current precautions for (2), (3),

(4), (5), (6) and (9). Delete Items (7) and (8). Advice on the recommended length of time before becoming pregnant is a medical issue to be discussed with a physician.

Pg 16, Section 2.3.2 Patient Precautions: Current Items a. (10) and Items b., c., and d. should be formatted as new paragraphs.

Pg 17, Section 2.3.2 Patient Precautions: Delete paragraph The release instructions may include measures that are necessary to limit the transfer of radioactive contamination as this information was presented in Item b.

Pg 17, Section 2.3.3 Patient Instruction, 1st paragraph: In 3rd sentence, add and/ after At that point, the patient. Add the following sentence after the 4th sentence, Consideration should be given to providing instructions at an 8th grade level of understanding, and with consideration given to native or primary language. Add the following sentence as the last sentence, Instruction should 6 of 8

also be provided on how long the precautions should be followed. As a guideline, the licensee may consider using several (3-5) effective half-lives of the administered therapeutic radionuclide.

Pg 17, Section 2.3.3 Patient Instructions: The list of specific patient instructions should be simplified to read:

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

b. Sleep alone in a separate bedroom.

c. Abstain from any intimate contact.

d. Avoid using public transportation.

e. Wash hands frequently and bath daily.

f. Wash laundry separately from others.

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

h. Use a dedicated sole use bathroom, if possible. Always sit on the toilet. Flush the toilet twice after each use.

i. Use disposable gloves and flushable wipes when cleaning.

j. Discard trash separately and/or hold it to allow for radioactive decay.

k. Avoid preparing or sharing food with others.

Pg 17-18, Section 2.3.3 Patient Instructions: The following specific patient instructions should be deleted as they are excessive, difficult to comply with, and will likely cause patient anxiety:

e. Shower 2-3 times a day for the first two days.

f. Try to empty your bladder at least every hour for the first 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months . Empty bladder at least once during the first night.

i. After five days of use, replace the tooth brush. The old one is to be placed with the trash being held for a month prior to disposal.

p. Wash linen, personal clothing, towels, etc. separately from those used by family members. A second rinse cycle is recommended.

Patient instruction o. Drink plenty of liquids (water, juice, tea, etc.) should be deleted as it may conflict with the patients medical condition. Excessive fluid intake has been reported to cause hyponatremia, which can cause seizures, coma, and even death.

Pg 19, Section 2.3.4 Patient Acknowledgment of Instructions, Item a: Add prior to treatment after treatment process.

Pg 19, Section 2.3.4 Patient Acknowledgment of Instructions, Item c (6): Change wording to read contact information if questions arise about the radiation safety instructions during the recovery period.

Pg 19, Section 2.4 Death of a Patient Following Radiopharmaceutical Administration or Implants, 1st sentence: Add the words administration of before a therapeutic quantity and delete the words of administration after therapeutic quantity.

Pg 20, Section 2.4 Death of a Patient Following Radiopharmaceutical Administration or Implants, 5th paragraph, 1st sentence: Add the words administration of before a therapeutic quantity and delete the words of administration after therapeutic quantity. Change the words body contains therapeutic quantities to body contains residual quantities.

7 of 8

Pg 20, Section 2.4 Death of a Patient Following Radiopharmaceutical Administration or Implants, 6th paragraph: Move the first sentence to the last sentence in the paragraph.

References

1. NRC Policy Issue (Information) SECY-18-0015, Staff Evaluation of the U.S. Nuclear Regulatory Commissions Program Regulation Patient Release After Radioisotope Therapy, January 29, 2018

2. ACMUI, Subcommittee Review and Comments on Draft Proposed Regulatory Guide 8.39, Release of Patients Administered Radioactive Materials, Revision 1 (Phase 1) Final Report, June 19, 2019

3. NRC Publication, Patient Release After Radionuclide Therapy - A review of the Technical Literature, Dose Calculations, and Recommendations, Reviewed by Shaheen Dewji and Nolan Hertel, September 25, 2017

4. IAEA Safety Reports Series No. 63, Release of Patients after Radionuclide Therapy, International Atomic Energy Agency, 2009

5. Smith,DS, Stabin MG, Exposure Rate Constants and Lead Shielding Values for Over 1,100 Radionuclides, Health Physics (102(3):271-291), 2012 Respectfully submitted, February 24, 2020, Subcommittee on Regulatory Guide 8.39 Release of Patients Administered Radioactive Materials, Advisory Committee on the Medical Use of Isotopes (ACMUI),

U.S. Nuclear Regulatory Commission (NRC) 8 of 8

U.S. NUCLEAR REGULATORY COMMISSION REGULATORY GUIDE 8.39 REVISION 1 Issue Date: December 2019 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 who have been administered unsealed byproduct material or implants that contain radioactive material. The RG provides licensees with instructions for patients before and after they receive medical procedures involving the administration of radioactive material, as well as requirements for recordkeeping. The RG also lists dose rates that should be used by licensees for the release of patients in order to meet NRC and Agreement State regulatory requirements.

Applicability This RG applies to all NRC and Agreement States medical licensees subject to Title 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 radiation safety of workers, the general public, patients, and human research subjects.

10 CFR 35.75 permits the licensee to authorize the release of any individual from its control who has been administered unsealed byproduct material or implants containing byproduct material if the total effective dose equivalent to any other individual from exposure to the released individual is not likely to exceed 5 millisieverts (mSv) (0.5 rem). 1

10 CFR 35.75(b) requires the licensee to provide the released individual or the individuals parent or guardian with instructions, including written instructions, on actions recommended to maintain doses to other individuals as low as is reasonably achievable (ALARA) if the total effective dose 1 The 5 millisieverts (mSv) (0.5 rem) release limit is a per administration of the patient and not a yearly limit.

Written suggestions regarding this guide or development of new guides may be submitted through the NRCs public Web site under the Regulatory Guides document collection of the NRC Library at http://www.nrc.gov/reading-rm/doc-collections/reg-guides/contactus.html .

Electronic copies of this regulatory guide, previous versions of this guide, and other recently issued guides are available through the NRCs public Web site under the Regulatory Guides document collection of the NRC Library at http://www.nrc.gov/reading-rm/doc-collections/.

The regulatory guide is also available through the NRCs Agencywide Documents Access and Management System (ADAMS) at http://www.nrc.gov/reading-rm/adams.html, under ADAMS Accession No. ML. The regulatory analysis may be found in ADAMS under Accession No. ML19108A462. The staff responses to the public comments on DG-8057 and the rest of the package may be found under ADAMS Accession No. ML19231A281.

equivalent 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) if the patient does not interrupt breastfeeding, the instructions shall also include (1) guidance on the interruption or discontinuation of breastfeeding and (2) information on the consequences of failure to follow the guidance.

10 CFR 35.75(c) requires the licensee to maintain a record of the basis for authorizing the release of an individual for 3 years after the date of release.

o 10 CFR 35.75(d) requires the licensee to maintain a record of instructions provided to a breastfeeding female for 3 years after the date of release.

o 10 CFR 35.2040, Records of written directives, provides a requirement for the length of time for keeping the written directives.

o 10 CFR 35.2063, Records of dosages of unsealed byproduct material for medical use, provides a requirement of the length of time for keeping the records on administered prescribed dosages. 2

10 CFR 35.2075, Release of individuals containing unsealed byproduct material or implants containing byproduct material, provides a requirement for a licensee to retain a record of the basis for authorizing the release of an individual.

Related Guidance

NUREG-1556, Consolidated Guidance about Materials Licenses: Program-Specific Guidance about Medical Use Licenses, Volume 9, Revision 3, issued September 2019 (Ref. 2)

NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material, issued February 1997 (Ref. 3)

Purpose of Regulatory Guides The NRC issues RGs to describe to the public methods that the staff 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 provide guidance to licensees. Regulatory guides are not substitutes for regulations and compliance with them is 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 guidance for implementing the information collections in 10 CFR Part 35 that are subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et seq.). These information collections were approved by the Office of Management and Budget (OMB), approval number 3150-0010. Send comments regarding this information collection to the Information Services Branch 2 Prescribed dosage(s), in accordance with 10 CFR Part 35.2, Definitions, means: The specified activity or range of activity of unsealed byproduct material as documented (1) in a written directive; or (2) in accordance with the directions of the authorized user for procedures performed pursuant to 10 CFR Part 35.100 and 35.200. The term dosage(s) in this RG is used to mean the prescribed dosage and is specified in terms of activity.

RG 8.39, Rev. 1, Page 2

(O-1F13), 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 (3150-0011 and 3150-0151), Attn: Desk Officer for the Nuclear 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 required to respond to, a collection of information unless the document requesting or requiring the collection displays a currently valid OMB control number.

RG 8.39, Rev. 1, Page 3

TABLE OF CONTENTS A. INTRODUCTION .................................................................................................................................. 1 B. DISCUSSION ......................................................................................................................................... 5 C. STAFF REGULATORY GUIDANCE .................................................................................................. 8

1. Release Criteria ........................................................................................................................ 8 1.1 Release of Patients Based on the Administered Activity ................................................. 8 1.2 Release of Patients Based on the Measured Dose Rate .................................................... 9 1.3 Release of Patients Based on Patient-Specific Dose Calculations ................................. 10

2. Instructions ............................................................................................................................. 10 2.1 Activities and Dose Rates That Require Instructions ................................................... 10 2.2 Additional Instructions for Release of Patients Who Could be Breastfeeding after Their Release ........................................................................................................ 11 2.3 Content of Instructions.................................................................................................. 14 2.3.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals ...... 14 2.3.2 Patient Precautions ............................................................................................ 15 2.3.3 Patient Instructions ............................................................................................ 17 2.3.4 Patient Acknowledgement of Instructions......................................................... 18 2.4 Death of a Patient Following Radiopharmaceutical or Implants Administrations........ 18

3. Records ................................................................................................................................... 20 3.1 Records of Release........................................................................................................ 20 3.2 Records of Instructions for Breastfeeding Patients ....................................................... 21

4. Summary Table ...................................................................................................................... 21 D. IMPLEMENTATION .......................................................................................................................... 22 REFERENCES ................................................................................................................................................ 23 APPENDIX A ................................................................................................................................................A-1 APPENDIX B ................................................................................................................................................ B-1 RG 8.39, Rev. 1, Page 4

B. DISCUSSION Reason for Revision This revision of the guide (Revision 1) provides licensees with more detailed instructions to patients before and after they have been administered radioactive material than was in Revision 0. In addition, the guide includes a new section on Death of a Patient Following Radiopharmaceutical or Implants Administrations, as well as additional guidance on requirements for recordkeeping.

Also, Table 3, Activities of Radiopharmaceuticals That Require Instructions and Records When Administered to Patients Who Are Breastfeeding an Infant or Child, has been revised to provide information for the recommended duration of interruption of breastfeeding to ensure that the dose to a nursing infant or child meets the NRC regulatory requirements.

The Commission directed the NRC staff in Staff Requirements Memorandum-COMAMM 0001/COMWDM-14-0001, Background and Proposed Direction to NRC Staff to Verify Assumptions Made Concerning Patient Release Guidance, to Revise Regulatory Guide 8.39, and subsequently NUREG-1556, Volume 9, to specify guidelines for patient information and instructional guidance.

Background

Title 10 of the Code of Federal Regulations (10 CFR) 35.75, Release of individuals containing unsealed byproduct material or implants containing byproduct material, often referred to as the Patient Release Rule, was promulgated in 1997. The NRC developed the subject regulation because the revision of 10 CFR Part 20 in 1991, which revised the dose limits for members of the general public in 10 CFR 20.1301, did not address exposure from the release of patients. The NRC determined that while doses should be maintained ALARA, a dose limit of 1 millisievert (mSv) (0.1 rem), or a dose limit of 5 mSv (0.5 rem) in certain circumstances, provides adequate protection. The 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 released individual, or the patients family or other caregivers, with appropriate instructions, including written 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 activities at which patients can be released were calculated by using, as a starting point, the method discussed in the National Council on Radiation Protection and Measurements (NCRP) Report No. 37, Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides, dated October 1, 1970 (Ref. 4). NCRP Report No. 37 uses the following equation to calculate the exposure until time t at a distance r from the patient:

0.693 34.6 (1 )

() = r2 (Equation 1)

Where D(t) = Accumulated exposure at time t, in roentgens 34.6 = Conversion factor of 24 hrs/day times the total integration of decay (1.44)

= Specific gamma ray constant for a point source, R/mCi-hr at 1 cm Q0 = Initial activity of the point source in millicuries, at the time of the release Tp = Physical half-life in days r = Distance from the point source to the point of interest in centimeters t = Exposure time in days RG 8.39, Rev. 1, Page 5

This guide uses the NCRP equation (Equation 1) in the following manner to calculate the activities at which patients may be released:

The dose to an individual likely to receive the highest dose from exposure to the patient is taken 0.693 to be the dose to total decay. Therefore, 1 is set equal to 1.

It is assumed that 1 roentgen is equal to 10 mSv (1 rem).

Appendix A to this guide provides the exposure rate constants and physical half-lives for radionuclides typically used in nuclear medicine and brachytherapy procedures.

Default activities at which patients may be released are calculated using the physical half-lives of the radionuclides and do not account for the biological half-lives of the radionuclides.

When a patients release is based on biological elimination (i.e., the effective half-life) instead of solely on the physical half-life of the radionuclide, Equation 1 is modified to account for the uptake and retention of the radionuclide by the patient, as discussed in Appendix B.

For radionuclides with a physical half-life greater than 1 day and for cases in which biological elimination is not considered, the assumption is that the individual who is likely to receive the highest dose from exposure to the patient would receive a dose of 25 percent of the dose to total decay (0.25 in Equation 2) at a distance of 1 meter. The selection of 25 percent of the dose to total decay at 1 meter for estimating the dose is based on the measurements discussed in the supporting regulatory analysis in NUREG-1492 that indicate that the dose calculated using an occupancy factor, E, of 25 percent at 1 meter is conservative in most normal situations.

For radionuclides with a physical half-life that is less than or equal to 1 day, justifying an occupancy factor of 0.25 is difficult because the relatively long-term averaging of behavior cannot be assumed. Under this situation, occupancy factors from 0.75 to 1.0 may be more appropriate.

Thus, for radionuclides with a physical half-life that is greater than 1 day, the following equation applies:

34.6 (0.25)

() = (100 cm)2 (Equation 2)

For radionuclides with a physical half-life less than or equal to 1 day and if an occupancy factor of 1.0 is used:

34.6 (1)

() = (100 cm)2 (Equation 3)

Equations 2 and 3 calculate the dose from external exposure to gamma radiation. These equations do not include the dose from internal intake by household members and members of the public because the dose from intake by other individuals is expected to be small for most radiopharmaceuticals (less than a few percent) relative to the external gamma-ray dose (see Appendix B, Section B-3). Further, the equations above do not apply to the dose to breastfeeding infants or children who continue to breastfeed.

Patients who are breastfeeding an infant or child must be considered separately, as discussed in Section RG 8.39, Rev. 1, Page 6

2.2 in Section C of this guide.

Harmonization with 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 standards for protecting people and the environment from harmful effects of ionizing radiation. These standards provide a system of safety fundamentals, safety requirements, and safety guides reflecting an international consensus on what constitutes a high level of safety. This system includes guidance to be considered for patient release.

IAEA, with contributions from the International Commission on Radiological Protection, has developed Safety Report Series No. 63 titled Release of Patients After Radionuclide Therapy, published in 2009 (Ref. 5). This report provides some practical guidance to Member States and the medical professionals involved in release of patients after therapy with unsealed radionuclides. The report addresses general guidance provided to patients after the administration of unsealed radioactive material, information to pregnant and breastfeeding women, and maximum dosages for patient release. The report references several of the documents that are also referenced in this DG as well as RG 8.39, version dated 1997. The instructions to patients included in the IAEA Safety Report Series No. 63 are similar to the instructions listed in DG 8.39.

RG 8.39, Rev. 1, Page 7

C. STAFF REGULATORY GUIDANCE This section describes in detail the methods, approaches, or data that the NRC staff considers acceptable for meeting the requirements of the applicable regulations cited in the introduction.

1. Release Criteria Licensees should use one of the following options to release a patient who has been administered radiopharmaceuticals or implants that contain radioactive material.

1.1 Release of Patients Based on the Administered Activity One means of complying with the dose limit in 10 CFR 35.75(a), licensees may release patients from licensee control if the dosage administered is not greater than the activity in Column 1 of Table 1.

The total effective dose equivalent is approximately equal to external dose because the portion of the internal dose that contributes to the total external dose exposure is small or negligible (see Appendix B, Section B-3). The activities in Table 1 are based on a total effective dose equivalent of 5 mSv (0.5 rem) to an individual using the following conservative assumptions:

a. administered activity;

b. physical half-life;

c. an occupancy factor of 0.25 at 1 meter for physical half-lives that are greater than 1 day and, for conservatism, an occupancy factor of 1 at 1 meter for physical half-lives that are less than or equal to 1 day; and

d. no shielding by tissue.

In this case, where the dosage administered is not greater than the activity in Column 1 of Table, no record of the release of the patient is required unless the patient is breastfeeding an infant or child, as discussed in Section 3.2 below.

If the activity administered exceeds the activity in Column 1 of Table 1, the licensee may release the patient when the activity has decayed to the activity in Column 1 of Table 1. In this case, 10 CFR 35.75(c) requires 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. The activities in Column 1 of Table 1 were calculated using either Equation 2 or 3 listed in section B. to this guide, depending on the physical half-life of the radionuclide.

If the licensee administers a radionuclide that is not listed in Table 1, it can demonstrate compliance with the regulation in 10 CFR 35.2075, Records of the release of individuals containing unsealed byproduct material or implants containing byproduct material, by maintaining a record of the calculation (for NRC inspection) of the release activity that corresponds to the dose limit of 5 mSv (0.5 rem). Additional guidance can be found in Section C.3 of this guide. Equation 2 or 3 (listed above) may be used, as appropriate, to calculate the activity, Q, corresponding to 5 mSv (0.5 rem).

The release activities in Column 1 of Table 1 do not consider the dose to a breastfeeding infant or child from the ingestion of radiopharmaceuticals 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.

In this case, it may be necessary to give instructions to the patient, as described in Staff Regulatory RG 8.39, Rev. 1, Page 8

Guidance Positions 2.2 and 2.3 below, as a condition for release. If failure to interrupt or discontinue breastfeeding could result in a dose to the nursing infant or child in excess of 5 mSv (0.5 rem), 10 CFR 35.2075(b) requires the licensee to maintain a record that the patient was given instructions. If a record is required, the licensee may demonstrate compliance by using the records of dosage described in 35.40, Written directives, which references 10 CFR 35.2040, Records of written directives, and 35.2063, Records of dosages of unsealed byproduct material for medical use.

1.2 Release of Patients Based on the Measured Dose Rate Licensees may release patients to whom radionuclides have been administered in amounts greater than the activities listed in Column 1 of Table 1 as long as the measured dose rate at 1 meter (from the surface of the patient) is no greater than the value in Column 2 of Table 1 for that radionuclide.

Table 1. Activities and Dose Rates for Authorizing Patient Releasea COLUMN 1 COLUMN 2 ACTIVITY AT OR BELOW DOSE RATE AT 1 METER, AT OR WHICH PATIENTS MAY BE BELOW WHICH PATIENTS MAY RELEASED BE RELEASEDb RADIONUCLIDE (GBq) (mCi) (mSv/h) (mrem/h)

Ag-111 19 520 0.08 8 Au-198 3.5 93 0.21 21 Cr-51 4.8 130 0.02 2 Cu-64 8.4 230 0.27 27 Cu-67 14 390 0.22 22 Ga-67 8.7 240 0.18 18 I-123 6.0 160 0.26 26 I-125 0.25 7 0.01 1 I-125 implant 0.33 9 0.01 1 I-131 1.2 33 0.07 7 In-111 2.4 64 0.2 20 Ir-192 implant 0.074 2 0.008 0.8 P-32 (c) (c) (c) (c)

Pd-103 implant 1.5 40 0.03 3 Re-186 28 770 0.15 15 Re-188 29 790 0.20 20 Sc-47 11 310 0.17 17 Se-75 0.089 2 0.005 0.5 Sm-153 26 700 0.3 30 Sn-117m 1.1 29 0.04 4 Sr-89 (c) (c) (c) (c)

Tc-99m 28 760 0.58 58 Tl-201 16 430 0.19 19 Yb-169 0.37 10 0.02 2

a. The activity values were computed based on a 5-mSv (0.5-rem) total effective dose equivalent.

b. 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) because the measurement includes shielding by tissue. See Staff Regulatory Guidance 3.1, Records of Release, for information on records.

RG 8.39, Rev. 1, Page 9

c. Activity and dose rate limits do not apply in this case because of the minimal exposures to members of the public resulting from dosages normally administered for diagnostic or therapeutic purposes.

NOTES: The millicurie (mCi) values in Table 1 were calculated using Equation 2 or 3 and the physical half-life. The gigabecquerel (GBq) values were calculated based on the mCi values and the conversion factor from mCi to GBq. The dose rate values were calculated based on the mCi values and the exposure rate constants. In general, the values were rounded to two significant figures. However, values less than 0.37 GBq (10 mCi) or 0.1 mSv (10 millirem (mrem)) per hour were rounded to one significant figure. NUREG-1492 describes the calculations in detail. Agreement State regulations may vary. Agreement State licensees should check their State regulations before using these values.

If a licensee administers a radionuclide that is not listed in Table 1 and if it chooses to release a patient based on the measured dose rate, it should first calculate a dose rate that corresponds to the 5-mSv (0.5-rem) dose limit. If the measured dose rate at 1 meter is no greater than the calculated dose rate, the patient may be released. The regulation at 10 CFR 35.2075(a) requires the licensee to maintain a record of the release. The dose rate at 1 meter may be calculated from Equation 2 or 3, as appropriate, because the dose rate at 1 meter is equal to Q per 10,000 square centimeters.

1.3 Release of Patients Based on Patient-Specific Dose Calculations Licensees may release patients based on dose calculations using patient-specific parameters.

With this method, in accordance with 10 CFR 35.75(a), the licensee must calculate the maximum likely dose to an individual exposed to the patient on a case-by-case basis. If the calculated maximum likely dose to an individual is no greater than 5 mSv (0.5 rem), the licensee may release the patient.

Using this method, licensees may be able to release patients with activities greater than those listed in Column 1 of Table 1 by accounting for the effective half-life of the radioactive material and other factors that may be relevant to the particular case. If the dose calculation considered retained activity, an occupancy factor 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.

Appendix B contains procedures for performing patient-specific dose calculations and describes how various factors may be considered in the calculations.

2. Instructions 2.1 Activities and Dose Rates That Require Instructions In accordance with 10 CFR 35.75(b), for some administrations, licensees must give instructions to the released patients, including written instructions, on how to maintain doses to other individuals ALARA after they are released. Licensees may use Column 1 of Table 2 to determine the dosage above which instructions must be given to patients. Column 2 provides corresponding dose rates at 1 meter based on the activities in Column 1. If the patient is breastfeeding an infant or child, additional instructions may be necessary (see Staff Regulatory Guidance Position 2.2).

Licensees may use the activities or dose rates in Table 2 to determine when they must give instructions to patients. When the licensee uses patient-specific calculations (as described in Appendix B),

it must give the patient instructions if the calculation indicates a dose that is greater than 1 mSv (0.1 rem).

If the licensee administers a radionuclide that is not listed in Table 2, it may calculate the activity or dose rate that corresponds to 1 mSv (0.1 rem) using Equation 2 or 3, as appropriate.

RG 8.39, Rev. 1, Page 10

Table 2. Activities and Dose Rates above Which Instructions Should Be Given When Authorizing Patient Releasea COLUMN 1 COLUMN 2 ACTIVITYABOVE WHICH DOSE RATE AT 1 METER ABOVE INSTRUCTIONS ARE REQUIRED WHICH INSTRUCTIONS ARE REQUIRED RADIONUCLIDE (GBq) (mCi) (mSv/h) (mrem/h)

Ag-111 3.8 100 0.02 2 Au-198 0.69 19 0.04 4 Cr-51 0.96 26 0.004 0.4 Cu-64 1.7 45 0.05 5 Cu-67 2.9 77 0.04 4 Ga-67 1.7 47 0.04 4 I-123 1.2 33 0.05 5 I-125 0.05 1 0.002 0.2 I-125 implant 0.074 2 0.002 0.2 I-131 0.24 7 0.02 2 In-111 0.47 13 0.04 4 Ir-192 implant 0.011 0.3 0.002 0.2 P-32 (b) (b) (b) (b)

Pd-103 implant 0.3 8 0.007 0.7 Re-186 5.7 150 0.03 3 Re-188 5.8 160 0.04 4 Sc-47 2.3 62 0.03 3 Se-75 0.018 0.5 0.001 0.1 Sm-153 5.2 140 0.06 6 Sn-117m 0.21 6 0.009 0.9 Sr-89 (b) (b) (b) (b)

Tc-99m 5.6 150 0.12 12 Tl-201 3.1 85 0.04 4 Yb-169 0.073 2 0.004 0.4

a. The activity values were computed based on a 1-mSv (0.1-rem) total effective dose equivalent.

b. Activity and dose rate limits are not applicable in this case because of the minimal exposures to members of the public resulting from dosages normally administered for diagnostic or therapeutic purposes.

NOTES: The mCi values in Table 2 were calculated using Equation 2 or 3 and the physical half-life. The GBq values were calculated based on mCi values and the conversion factor from mCi to gBq. The dose rate values were calculated based on mCi values and exposure rate constants. In general, values are rounded to two significant figures. However, values less than 0.37 GBq (10 mCi) or 0.1 mSv (10 mrem) per hour are rounded to one significant figure. NUREG-1492 describes the calculations in detail.

Agreement State regulations may vary. Agreement State licensees should check their State regulations before using these values.

2.2 Additional Instructions for Release of Patients Who Could Be Breastfeeding after Their Release The requirement in 10 CFR 35.75(b) that a licensee must give the patient instructions presumes that the licensee will ask the patient, as appropriate, about her breastfeeding status. The purpose of the instructions, including guidance on interruption or discontinuation of breastfeeding, is to permit licensees to release a patient who could be breastfeeding an infant or child when the dose to the infant or child could exceed 1 mSv (0.1 rem) if the patient does not interrupt breastfeeding.

RG 8.39, Rev. 1, Page 11

If the patient could be breastfeeding an infant or child after release and if the patient was administered a radiopharmaceutical with an activity above the value stated in Column 1 of Table 3, the licensee should give the patient instructions on the discontinuation or interruption period for breastfeeding and the potential consequences of failing to follow the recommendation. The patient should also be informed if breastfeeding would not likely result in consequences for the infant or child. Table 3 also provides the recommended duration (Column 3) of interrupting or discontinuing breastfeeding to minimize the dose to below 1 mSv (0.1 rem) if the patient has received certain radiopharmaceutical doses (Column 1). Table 3 lists the radiopharmaceuticals that are commonly used in medical diagnosis and treatment.

If the licensee administers a radiopharmaceutical that is not listed in Table 3 to a patient who could be breastfeeding, it should evaluate whether instructions or records (or both) are required. The licensee can calculate the dose to the infant or child by using the dose conversion factors given for a newborn infant by M. Stabin, Internal Dosimetry in Pediatric Nuclear Medicine (Ref. 6) and maintain a record of the calculation as required by 10 CFR Part 35.2075(b).

If additional instructions are required because the patient is breastfeeding, the instructions should include appropriate recommendations on whether to interrupt breastfeeding; the length of time to interrupt breastfeeding; or, if necessary, the discontinuation of breastfeeding. The instructions should inform the patient of the consequences of failure to follow the recommendation to interrupt or discontinue breastfeeding. The licensee should explain the consequences 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 consequence of procedures involving iodine (I)-131 is that continued breastfeeding could harm the infants or childs thyroid.

Table 3. Activities of Radiopharmaceuticals That Require Instructions and Records When Administered to Patients Who Are Breastfeeding an Infant or Child COLUMN 1 COLUMN 2 COLUMN 3 ACTIVITY ACTIVITY EXAMPLES OF ABOVE WHICH ABOVE WHICH RECOMMENDED INSTRUCTIONS A RECORD IS DURATION OF ARE REQUIRED REQUIRED INTERRUPTION OF RADIOPHARMACEUTICAL (MBq) (mCi) (MBq) (mCi) BREASTFEEDINGa I-131 NaI 0.01 0.0004 0.07 0.002 Complete cessation (for this infant or child)

I-123 NaI 20 0.5 100 3 3 daysb I-123 OIH 100 4 700 20 I-123 MIBG 70 2 400 10 24 hours2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months for 370 MBq (10 mCi)

I-125 OIH 3 0.08 15 0.4 I-131 OIH 10 0.30 60 1.5 Tc-99m DTPA 1,000 30 6,000 150 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m MAA 50 1.3 200 6 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m Pertechnetate 100 3 600 15 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m DISIDA 1,000 30 6,000 150 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m Glucoheptonate 1,000 30 6,000 150 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m HAM 400 10 2,000 50 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m MIBI 1,000 30 6,000 150 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m MDP 1,000 30 6,000 150 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m PYP 900 25 4,000 120 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb RG 8.39, Rev. 1, Page 12

COLUMN 1 COLUMN 2 COLUMN 3 ACTIVITY ACTIVITY EXAMPLES OF ABOVE WHICH ABOVE WHICH RECOMMENDED INSTRUCTIONS A RECORD IS DURATION OF ARE REQUIRED REQUIRED INTERRUPTION OF RADIOPHARMACEUTICAL (MBq) (mCi) (MBq) (mCi) BREASTFEEDINGa Tc-99m Red Blood Cell In Vivo 400 10 2,000 50 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Labeling Tc-99m Red Blood Cell In Vitro 1,000 30 6,000 150 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Labeling Tc-99m Sulphur Colloid 300 7 1,000 30 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m DTPA 1,000 30 6,000 150 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m DTPA Aerosol 1,000 30 6,000 150 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m MAG3 1,000 30 6,000 150 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Tc-99m White Blood Cells 100 3 600 15 24 hour2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months sb Ga-67 1 0.04 7 0.2 28 daysb Cr-51 EDTA 60 1.6 300 8 In-111 White Blood Cells 10 0.2 40 1 6 daysb Tl-201 Chloride 40 1 200 5 4 daysb C-11, N-13, O-15, Rb-82 No interruptionb F-18 FDG 4 hour4.62963e-5 days 0.00111 hours 6.613757e-6 weeks 1.522e-6 months sb Lu-177 Octreotate , diagnostic or Complete cessation (for therapeutic The activity to the infant or child can be this infant or child) b Ra-223 and all alpha emitters calculated by using the dose conversion Complete cessation (for factors given by M. Stabin, Internal this infant or child) b Zr-89 Dosimetry in Pediatric Nuclear Medicine 28 daysb Ga-68 Octreotate (Ref. 6). 4 hour4.62963e-5 days 0.00111 hours 6.613757e-6 weeks 1.522e-6 months sb In-111 Octreotate 6 daysb I-124 NaI Complete cessation (for this infant or child)b

a. The duration of interruption of breastfeeding is selected to reduce the maximum dose to a newborn infant to less than 1 mSv (0.1 rem), although the regulatory limit is 5 mSv (0.5 rem). The actual doses that most infants would receive would be far below 1 mSv (0.1 rem). The physician may use discretion to recommend increasing or decreasing the duration of interruption as long as his or her instructions would ensure that the dose to the child is less than the regulatory limit of 5 mSv (0.5 rem).

b. These recommendations on the interruption or discontinuation of breastfeeding are from the ACMUI Subcommittee on Nursing Mother Guidelines for the Medical Administration of Radioactive Materials. (Ref. 7) If there is no recommendation in Column 3 of this Table, the maximum activity normally administered is below the activities that require instructions on interruption or discontinuation of breast-feeding. (For Tc-99m labeled radiopharmaceuticals, rather than a radiopharmaceutical-specific interruption period, a single 24-hour interruption period is recommended. Although this time interval may be longer than necessary for some Tc-99m labeled radiopharmaceuticals, it is compliant with the 0.1-rad dose limit and simplifies the guidance, thereby avoiding confusion and reducing the likelihood of error.)

NOTES: Activities are rounded to one significant figure, except when the use of two significant figures was considered appropriate. NUREG-1492 describes the calculations in detail Agreement State licensees should check with their State regulations before using the values on the Table.

RG 8.39, Rev. 1, Page 13

2.3 Content of Instructions This section describes different aspects that the licensee should consider when developing patient release instructions before and after a patients treatment. Generally, when a licensee releases a patient, it is to the patients home where family or other caregivers may be present. To provide adequate release instructions under 10 CFR 35.75(b), the licensee should consider the patients destination upon his or her release and the ability of the patient or caregiver to understand and follow the release instructions. The licensee should thoroughly ascertain the patients posttreatment destination and the method by which he or she plans to travel to that destination to best estimate the likely cumulative radiation exposures to other members of the public (e.g., family and other caregivers) and, therefore, to direct appropriate protective measures to keep doses ALARA and ensure that the dose limit will likely be met.

I-131 is the medical radioisotope of highest concern, as it is the most commonly used radionuclide in radiopharmaceutical therapy and has the potential for a higher external exposure to members of the public because of its high-energy gamma emission and potential volatility (Ref. 8).

However, the regulations in 10 CFR 35.75 apply to other medical radioisotope therapies such as phosphorus (P)-32, strontium (Sr)-89, 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 individual situations. Note that instructions should not interfere with or contradict the best medical judgment of the treating physician. The instructions should include the name of a knowledgeable person and his or her telephone number for the patient to contact with any questions.

2.3.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals Engaging the patient early in the treatment process (i.e., during treatment planning) may help the licensee better familiarize the patient and caregiver with the treatment procedures, posttreatment radiation safety precautions, and protective measures to minimize radiation exposure to other individuals. This discussion should also include medical issues such as complications, side effects, and dietary and medication changes, as appropriate. Additionally, early engagement with the patient allows the patient to ask the licensee questions that will help him or her comply with the release instructions. It also helps the licensee to determine whether the patient will be able to follow the release instructions.

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 assess the patients specific circumstances. The licensee and patient or caregiver should discuss and consider the following topics during the pretreatment discussion:

a. What type of posttreatment lodging (e.g., group home, apartment, townhome, detached single family home) 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, or public transportation (i.e., bus, train, or airplane)? The use of public transportation should be discouraged, if possible.

(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 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 airplanes are subject to screening RG 8.39, Rev. 1, Page 14

for radiation. Patients should be advised of this fact and provided appropriate documentation (procedure, isotope, date/time of release, treating 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 household after treatment?

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

f. Is the patient incontinent?

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

h. Are there any factors that might prevent treatment (e.g., breastfeeding, pregnancy)?

i. Are there any concerns about breastfeeding or pregnancy?

j. What are the consequences if the patient does not follow the release instructions?

k. Can the patient delay returning to work?

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

By gathering this information before the treatment (i.e., during the treatment planning stage), the licensee can modify assumptions used in its release calculations, as necessary, to (1) provide a patient-specific estimate of the likely cumulative dose to other members of the public, (2) direct appropriate protective measures, and (3) allow the patient time to plan for his or her potential isolation after release. It will also allow the licensee to assess the patients capacity to understand the procedure and precautions.

2.3.2 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 at or below the 5-mSv (0.5-rem) limit. The patient precautions listed on pages 15 through 17 are topics that should be considered by the licensee, therefore not requirements by the NRC. The license should use judgement with the instructions needed for the patient on a case-by-case basis based on the treatment.

a. 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. If the patient is traveling with other individuals to the post treatment lodging location, emphasis should be made to minimize the number of traveling companions and to maximize the distance from the patient.

(1) Emphasize the importance of keeping an adequate distance from others, especially children and pregnant women. Can arrangements be made for family members (including RG 8.39, Rev. 1, Page 15

children and any pregnant household 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) Encourage the patient not to prepare or share food with others.

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

(4) 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 use disposable eating utensils.

(5) Encourage the use of disposable gloves, flushable wipes, and frequent hand washing.

(6) Encourage the laundering of a patients clothing separately from other household members clothing.

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

(8) Advise the patient on the recommended length of time he or she should wait before becoming pregnant to minimize radiation exposures to a developing fetus.

(9) Discuss how to clean up an area contaminated with body fluids (e.g., urine, vomit).

(10) Evaluate the need to dispose of patient-related trash in a separate strong plastic bag that is not mixed with other household members 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 radioactive decay may be important if the landfill may detect the radiation and send the trash back to the patient.

b. Discuss how the patient may contact the licensee if needed. Provide information to a family member or caregiver to contact the treatment medical facility if the patient has a medical emergency or passes away.

c. In the case of a medical emergency, the patient, or a caregiver, should inform the ambulance or the emergency care location of the recentness of the radioactive therapy treatment.

d. Provide posttreatment release instructions to the patient verbally and in writing, including how long he or she should follow the release instructions.

If the patient or caregiver is mentally or physically unable to comply with the release instructions, the licensee may have to consider holding the patient as an inpatient following treatment until the patient can be released without having to follow any specific instructions. Similarly, if the licensee determines that the patients posttreatment plans, including any instructions that it believes the patient cannot follow, planned mode of transportation, and posttreatment destination, are likely to cause a dose to other individuals that will exceed 5 mSv (0.5 rem), the licensee may not release the patient until the dose to other individuals is not likely to exceed 5 mSv (0.5 rem).

The release instructions may include measures that are necessary to limit the transfer of radioactive contamination to others. The licensee may encourage patients to have available plastic bags, disposable gloves, and flushable wipes before treatment. The licensee should provide specific information on how to RG 8.39, Rev. 1, Page 16

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 how to minimize, isolate, and clean radioactive contamination is important in minimizing exposure to 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 advance in accordance with 10 CFR 35.3047, Report and Notification of a Dose to an Embryo/Fetus or a Nursing Child.

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

2.3.3 Patient Instructions The licensee must comply with 10 CFR 35.75 by ensuring that the radiation dose to other individuals is not likely to exceed 5 mSv (0.5 rem) from a released patient who has been administered radiopharmaceuticals or permanent implants that contain radioactive material. However, once a patient is released, the licensee has no control of the patient. At that point, the patient or caregiver assumes responsibility for managing radiation exposure to other individuals based on the release instructions provided by the licensee. The instructions should be easy to follow to enable the patient to understand how to minimize radiation exposure to other individuals (Ref. 9). For most therapies, experience shows that radiation exposure from patients can be safely controlled through appropriate treatment -specific release instructions provided by licensees and followed by patients. The list below provides some basic posttreatment instructions that the patient may need to follow for managing radiation exposure to other individuals. The instructions should always be tailored to the specific patient situation and type and amount of radioactive material administered or implanted.

a. Wash his or her hands frequently.

b. Shower 2 - 3 times a day for the first two days.

c. Wash his or her laundry separately from other peoples laundry.

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

e. Use a bathroom reserved exclusively for him or her, if possible. Always sit on the toilet and try to empty your bladder at least once every hour for the first 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months . Empty bladder at least once during the first night. Flush the toilet twice to remove any radioactivity from the toilet bowl.

f. Use disposable gloves and flushable wipes when cleaning.

g. Discard his or her trash separately and hold it to allow for radioactive decay.

h. After five days of use, replace the toothbrush. The old one is to be placed with the trash being held for a month prior to disposal.

RG 8.39, Rev. 1, Page 17

i. Sleep alone.

j. Abstain from all forms of intimate contact.

k. Avoid preparing or sharing food with others. If choosing to prepare food for others, consider using gloves while cooking.

l. Avoid using public transportation, if possible.

m. Minimize the amount of time spent near other people, especially children and pregnant women.

n. Drink plenty of clear liquids (water, juice, tea, etc.)

o. Wash linen, personal clothing, towels, etc. separately from those items used by family members.

A second rinse cycle is recommended.

The licensee should instruct family members and caregivers to notify the treating medical facility of a medical emergency or if a patient dies. The licensee should also tell the patient how to clean up an area contaminated with body fluids (e.g., urine, vomit).

2.3.4 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 instructions as communicated using a form signed by both parties. Through the form, the patient acknowledges the receipt of the following:

a. He or she has received a clear explanation of the treatment process.

b. He or she has been informed of the need to limit exposure to others, 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 plans 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 at 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 name and telephone number of a knowledgeable person) if questions arise during the recovery period.

2.4 Death of a Patient Following Radiopharmaceutical Administration or Implants If the licensee learns that a patient has died shortly after a therapeutic quantity of administration RG 8.39, Rev. 1, Page 18

of radioactive material, the treating authorized user and the radiation safety office (RSO), should be notified immediately. The RSO, or authorized user should perform an assessment of the type and amount of retained activity, based on the patient records.

If the death occurs in a hospital, access to the room occupied by the deceased should be controlled until the room has been surveyed, and decontaminated if necessary. A specified form of patient identifier (e.g., bracelet, body tag) should be attached with relevant information to the radioactive body. A body bag may need to be used to contain the leakage of radioactive material. To minimize external radiation, the body may need to be retained in a secured area. Radiation safety procedures to be applied in practice for handling the body should be determined in close consultation with the RSO and an authorized user at the facility where the therapy was administered. If a patient is subsequently admitted to a different hospital or facility after release and then passes away, the local RSO should be involved.

Unsealed radioactive material may be present in a particular body cavity or organ, or it may have concentrated after systemic administration (e.g., I-131 in the thyroid gland). Drainage of the cavity or excision of the organ will reduce exposure if undertaken at the start of the autopsy. In addition, care should be given with respect to organs with significant activity. If the patient had received a dose of beta-emitting colloid or spheres (e.g., P-32 chromic phosphate into a body cavity, Y-90 microspheres into the liver), significant activity may be present in the cavity fluid or in the organ. Beta radiation sources may provide a significant dose to the hands because they will be in close contact with body tissues and fluids (Ref. 10).

Autopsy and pathology staff should wear standard protective clothing (i.e., gloves, laboratory coats, and eye protection), and personnel monitoring should be considered, if significant activity of photon emitting radionuclides are involved. For beta emitters, double surgical gloves may help reduce skin exposures. Wearing a face shield or eye protection and a face mask can prevent an intake of airborne material inadvertently released during the cutting or movement of radioactive tissue or organs.

When an RSO has been notified that a patient has died shortly after a therapeutic quantity of administration of radioactive material, the RSO should notify the morgue or funeral home that the body contains therapeutic quantities of radioactive material and provide precautions to minimize radiation exposures and radioactive contamination for embalming and burial or cremation. These include the use of gloves and protective clothing and proper cleaning of equipment.

Cremation may not be allowed based on local regulations and the RSO should consult with local authorities prior to making cremation arrangements. If the body is to be cremated, the RSO should provide precautions on handling the body to crematorium employees who may receive external exposure from the radioactive body or from contamination of the crematorium or internal exposure from inhalation of radioactive particles while handling the ashes. A proportion of the activity retained will appear in cremated remains and may be a concern, particularly in the case of long-lived radionuclides, that will require specified controls. The main concern is in regard to the scattering of ashes, although contact dose rates with the container may have to be considered if cremation takes place shortly after administration of the treatment.

Cremation of nonvolatile radionuclides might result in contamination of the furnace. Because workers could potentially inhale contaminated ash particles while cleaning the furnace, workers should wear dust masks and protective garments while cleaning the furnace. The most likely hazard to the general population near the crematorium is the inhalation of radioactive material emitted with the stack gases.

RG 8.39, Rev. 1, Page 19

The RSO should be consulted to determine the amount of activity remaining in the deceased patient and a determination should be made if there are any state or municipal restrictions on cremation.

a. If the activity remaining in the body is greater than regulatory limits or if regulatory limits have not been established, the RSO should determine the radiation precautions that should be followed.

b. Precautions should be based on dose limits, a generic safety assessment of the need for monitoring personnel who carry out these procedures, the need for monitoring the premises, the need for minimizing external radiation exposure, and the potential for contamination (Ref. 10).

c. Precautions should to be taken to protect family members and the general public during visitation prior to burial or internment.

3. Records 3.1 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 occupancy 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. This record should include the patients identifier in a way that ensures that confidential patient information is not traceable or attributable to a specific patient, the radioactive material administered, the administered dosage, and the date of the administration. In addition, depending on the basis for authorizing the release of patients, records should include the following information:

a. For Immediate Release of a Patient Based on a Patient-Specific Calculation. The record should include the equation used, including the patient-specific factors and the bases used in calculating the dose to the person exposed to the patient and the calculated dose. The patient-specific factors (see Appendix B to this guide) include the effective half-life and uptake fraction for each component of the biokinetic model, the time that the physical half-life was assumed to apply to retention, and the occupancy factor. The record should include the basis for the selection of each of these values.

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.

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 time of release, and the results of the decay calculation.

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.

In some situations, a calculation may be case specific for a class of patients who all have the same patient-specific factors. In this case, the record for a particular patients release may reference the calculation for the class of patients.

RG 8.39, Rev. 1, Page 20

Records should be kept in a manner that ensures the patients confidentiality (i.e., the records should not contain the patients name but instead a patient identification number, date, and treatment type). Records should be kept in a manner that ensures the patient's privacy/confidentiality. These recordkeeping requirements may also be used to verify that licensees have proper procedures in place for assessing potential third-party exposure associated with and arising from exposure to patients administered radioactive material.

3.2 Records of Instructions for Breastfeeding Patients If a patients failure to interrupt or discontinue breastfeeding 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 2 of Table 3 lists the activities that require such records when administered to patients who are breastfeeding.

The record should include the patients identifier, the radiopharmaceutical administered, the administered dosage, the date of the administration, and whether instructions were provided to the patient who could be breastfeeding an infant or child. The patients identifier should be prepared in a way that would ensure that confidential information is not traceable or attributable to a specific patient.

4. Summary Table Table 4 summarizes the criteria for releasing patients and the requirements for providing instructions and maintaining records.

Table 4. Summary of Release Criteria, Required Instructions to Patients, and Records To Be Maintained PATIENT BASIS FOR CRITERIA FOR INSTRUCTIONS RELEASE RECORDS GROUP RELEASE RELEASE NEEDED? REQUIRED?

All patients, Administered Administered Yes, if administered No including activity activity activity > Column 1 of patients who Column 1 of Table 2 are breast- Table 1 feeding an Retained Retained activity Yes, if retained activity Yes infant or child activity Column 1 of > Column 1 of Table 2 Table 1 Measured dose Measured dose Yes, if dose rate Yes rate rate Column 2 > Column 2 of Table 2 of Table 1 Patient-specific Calculated dose Yes, if calculated dose Yes calculations 5 mSv (0.5 rem) > 1 mSv (0.1 rem)

Patients who All the above All of the above Additional instructions Records that instructions are breast- bases for bases for release required if were provided if feeding an release administered dosage administered dosage infant or child > Column 1 of Table 3 > Column 2 of Table 3 or or licensee-calculated licensee-calculated dose dose from from continued breastfeeding > 1 mSv breastfeeding > 5 mSv (0.1 rem) to the infant (0.5 rem) to the infant or or child child RG 8.39, Rev. 1, Page 21

D. IMPLEMENTATION The NRC staff may use this regulatory guide as a reference in its regulatory processes, such as licensing, inspection, or enforcement. Backfitting, forward fitting, 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 provisions and the forward fitting policy in Management Directive 8.4, Management of Backfitting, Forward Fitting, Issue Finality, and Information Requests, (Ref. 11) does not apply to these licensees. In addition, backfitting, forward fitting, and issue finality considerations do not apply to 10 CFR Part 35 licensees and applicants because they are using the guidance in this regulatory guide to demonstrate compliance with the requirements in 10 CFR Part 35.

RG 8.39, Rev. 1, Page 22

REFERENCES 3

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, Consolidated Guidance about Materials Licenses: Program-Specific Guidance about Medical Use Licenses, Volume 9, Revision 3, Washington, DC, September 2019.

3. NRC, NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material, Washington, DC, February 1997.

4. National Council on Radiation Protection and Measurements (NCRP) Report No. 37, Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides, Bethesda, MD, October 1, 1970. 4

5. International Atomic Energy Agency, Release of Patients after Radionuclide Therapy, Safety Reports Series No. 63, Vienna, Austria, 2009. 5

6. Stabin, M., Internal Dosimetry in Pediatric Nuclear Medicine, Pediatric Nuclear Medicine, S. Treves (Editor), Springer Verlag, New York, NY, pp. 556-581, 1995.

7. NRC, Advisory Committee on the Medical Uses of Isotopes (ACMUI), Nursing Mother Guidelines for the Medical Administration of Radioactive Materials, Washington, DC, January 31, 2019. (Agencywide Documents Access and Management System (ADAMS) Accession No. ML19038A498).

8. NRC, SECY-18-0015, Staff Evaluation of the U.S. Nuclear Regulatory Commissions Program Regulating Patient Release after Radioisotope Therapy, Washington, DC, January 29, 2018.

(ADAMS Accession No. ML17279B139 (package)).

9. NRC, Advisory Committee on the Medical Uses of Isotopes, Patient Release Report, Washington, DC, December 13, 2010. (ADAMS Accession No. ML103481099).

10. NCRP Report No. 155, Management of Radionuclide Therapy Patients, Bethesda, MD, December 11, 2006.

3 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.

4 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.

5 Copies of International Atomic Energy Agency (IAEA) documents may be obtained through its Web site at WWW.IAEA.Org/ or by writing the International Atomic Energy Agency, P.O. Box 100 Wagramer Strasse 5, A 1400 Vienna, Austria; telephone (+431) 2600-0; fax (+431) 2600-7; or e mail Official.Mail@IAEA.Org.

RG 8.39, Rev. 1, Page 23

APPENDIX A TABLE A-1. HALF-LIVES AND EXPOSURE RATE CONSTANTS OF RADIONUCLIDES USED IN MEDICINE EXPOSURE EXPOSURE RATE RATE HALF - CONSTANTb HALF - CONSTANTb LIFE (R/mCi-h at 1 LIFE (R/mCi-h at RADIONUCLIDE (days)a cm) RADIONUCLIDE (days)a 1 cm)

Ag-111 7.45 0.150 Pd-103 implant 16.96 0.86d Au-198 2.696 2.3 Re-186 3.777 0.2 Cr-51 27.704 0.16 Re-188 0.708 0.26 Cu-64 0.529 1.2 Sc-47 3.351 0.56 Cu-67 2.578 0.58 Se-75 119.8 2.0 Ga-67 3.261 0.753 Sm-153 1.946 0.425 I-123 0.55 1.61 Sn-117m 13.61 1.48 I-125 60.14 1.42 Sr-89 50.5 NAe I-125 implant 60.14 1.11c Tc-99m 0.251 0.756 I-131 8.04 2.2 TI-201 3.044 0.447 In-111 2.83 3.21 Y-90 2.67 NAe Ir-192 implant c 74.02 4.594 Yb-169 32.01 1.83 P-32 14.29 NAe

a. See K.F. Eckerman, A.B. Wolbarst, and A.C.B. Richardson, Federal Guidance Report No. 11: Limiting Values of Radionuclide Intake and Air Concentration and Dose Conversion Factors for Inhalation, Submersion, and Ingestion, Report No. EPA-520/1-88-020, Office of Radiation Programs, U.S. Environmental Protection Agency, Washington, DC, issued September 1988 (Ref. A-1).

b. Values for the exposure rate constant for gold (Au)-198, chromium (Cr)-51, copper (Cu)-64, iodine (I)-131, scandium (Sc)-

47, and selenium (Se)-75 are from page 135 of the Radiological Health Handbook issued by the U.S. Department of Health, Education, and Welfare in 1970 (Ref. A-2). For Cu- 67, I-123, indium (In)-111, rhenium (Re)-186, and Re-188, the values for the exposure rate constant are from NUREG/CR-4444, Radiation Safety Issues Related to Radiolabeled Antibodies, issued 1991 (Ref. A-3). For silver (Ag)-111, gallium (Ga)-67, I-125, samarium (Sm)-153, tin (Sn)-117m, technetium (Tc)-99m, thallium (T1)-201, and ytterbium (Yb)-169, the exposure rate constants were calculated because the published values for these radionuclides were either an approximation, presented as a range, or varied from one reference to another. Table A.2 of Appendix A to NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material, issued February 1997, shows the calculation of the exposure rate in detail (Ref. A-4).

c. See R. Nath, A.S. Meigooni, and J.A. Meli, Dosimetry on Transverse Axes of 125I and 192Ir Interstitial Brachytherapy Sources, Medical Physics, 17(6):1032-1040, issued November 1990. The exposure rate constant given is a measured value averaged for several source models and accounts for the attenuation of gamma rays within the implant capsule (Ref. A-5).

d. See A.S. Meigooni S. Sabnis, and R. Nath, Dosimetry of Palladium-103 Brachytherapy Sources for Permanent Implants, Endocurietherapy Hyperthermia Oncology, Volume 6, issued April 1990. The exposure rate constant given is an apparent value (i.e., with respect to an apparent source activity) and accounts for the attenuation of gamma rays within the implant capsule (Ref. A-6).

e. Radionuclide is a pure beta emitter (and there is no single exposure rate constant associated with the secondary bremsstrahlung radiation applicable for such radionuclides).

RG-8.39, Rev. 1, Appendix A, Page A-1

REFERENCES FOR APPENDIX A 6 A-1. K.F. Eckerman, A.B. Wolbarst, and A.C.B. Richardson, Federal Guidance Report No. 11:

Limiting Values of Radionuclide Intake and Air Concentration and Dose Conversion Factors for Inhalation, Submersion, and Ingestion, Report No. EPA-520/1-88-020, Office of Radiation Programs, U.S. Environmental Protection Agency, Washington, DC, issued in September 1988.

A-2. Radiological Health Handbook, U.S. Department of Health, Education, and Welfare, 1970.

A-3. NUREG/CR-4444, Radiation Safety Issues Related to Radiolabeled Antibodies, issued in 1991.

A-4. NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material, issued in February 1997.

A-5. R. Nath, A.S. Meigooni, and J.A. Meli, Dosimetry on Transverse Axes of 125I and 192Ir Interstitial Brachytherapy Sources, Medical Physics, 17(6):1032-1040, issued in November 1990.

A-6. A.S. Meigooni S. Sabnis, and R. Nath, Dosimetry of Palladium-103 Brachytherapy Sources for Permanent Implants, Endocurietherapy Hyperthermia Oncology, Volume 6, issued in April 1990.

6. 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. 1, Appendix A, Page A-2

APPENDIX B PROCEDURES FOR CALCULATING DOSES BASED ON PATIENT-SPECIFIC FACTORS A licensee may release a patient who has been administered a dosage higher than the values listed in Column 1 of Table 1 of this regulatory guide if dose calculations using patient-specific parameters, which are less conservative than the conservative assumptions, show that the total effective dose equivalent to any individual is not likely to be greater than 5 millisieverts (mSv) (0.5 rem).

If the release of a patient is based on a patient-specific calculation that considered the retained activity, an occupancy factor of less than 0.25 at 1 meter, the effective half-life, or shielding by tissue, Title 10 of the Code of Federal Regulations (10 CFR) 35.2075(a) requires the licensee to maintain a record of the basis for authorizing the release.

The following equation can be used to calculate doses:

34.6 (1 0.693t )

() = r2 (Equation B-1) where D(t) = Accumulated exposure at time t, in rem 34.6 = conversion factor of 24 hours2.777778e-4 days 0.00667 hours 3.968254e-5 weeks 9.132e-6 months per day times total integration of decay (1.44)

= exposure rate constant for a point source, R/mCi x hr at 1 centimeter (cm)

Q0 = initial activity at the start of the time interval Tp = physical half-life in days E = occupancy factor that accounts for different occupancy times and distances when an individual is near a patient r = distance in centimeters (this value is typically 100 cm) t = exposure time in days B-1. Occupancy Factor B-1.1 Rationale for Occupancy Factors Used to Derive Table 1 of Regulatory Guide 8.39 In Table 1 of this regulatory guide, the activities at which patients could be released were calculated using the physical half-life of the radionuclide and an occupancy factor at 1 meter of either 0.25 (if the radionuclide has a half-life longer than 1 day) or 1.0 (if the radionuclide has a half-life less than or equal to 1 day). The basis for the occupancy factor of 0.25 at 1 meter is that measurements of doses to family members and considerations of normal human behavior (as discussed in the supporting regulatory analysis (Ref. B-1)) suggest that an occupancy factor of 0.25 at 1 meter, when used in combination with the physical half-life, will produce a generally conservative estimate of the dose to family members when instructions on minimizing doses to others are given.

RG-8.39, Rev. 1, Appendix B, Page B-6

An occupancy factor of 0.25 at 1 meter is not considered appropriate when the physical half-life is less than or equal to 1 day, and therefore, the dose is delivered over a short time. Specifically, the assumptions about patient behavior that led to an occupancy factor of 0.25 at 1 meter include the assumption that the patient will not be in close proximity to other individuals for several days. However, when the dose is from a short-lived radionuclide, the time that individuals spend in close proximity to the patient immediately following his or her release will be most significant because the dose to other individuals could be a large fraction of the total dose from the short-lived radionuclide. Therefore, to be conservative when providing generally applicable release quantities that may be used with little consideration of the specific details of a particular patients release, the values calculated in Table 1 of this regulatory guide were based on an occupancy factor of 1 at 1 meter when the half-life is less than or equal to 1 day.

B-1.2 Occupancy Factors To Consider for Patient-Specific Calculations The selection of an occupancy factor for patient-specific calculations will depend on whether the physical or effective half-life of the radionuclide is used and whether instructions are given to the patient before his or her release. Patient-specific calculations may use the following occupancy factors, E, at 1 meter:

a. E = 0.75 when a physical half-life, an effective half-life, or a specific time period under consideration (e.g., bladder-holding time) is less than or equal to 1 day.

b. E = 0.25 when an effective half-life is greater than 1 day if the patient has been given the following instructions:

(1) Maintain a prudent distance from others for at least the first 2 days.

(2) Sleep alone in a room for at least the first night.

(3) Do not travel by airplane or public transportation for at least the first day.

(4) Do not travel on a prolonged automobile trip with others for at least the first 2 days.

(5) Have sole use of a bathroom for at least the first 2 days.

(6) Drink plenty of fluids for at least the first 2 days.

c. E = 0.125 when an effective half-life is greater than 1 day if the patient has been given the following instructions:

(1) Follow the instructions for E = 0.25 above.

(2) Live alone for at least the first 2 days.

(3) Have few visits by family or friends for at least the first 2 days.

d. In a two-component model (e.g., uptake of iodine (I)-131 using thyroidal and extrathyroidal components), if the effective half-life associated with one component is less than or equal to 1 day but is greater than 1 day for the other component, it is more justifiable to use the occupancy factor associated with the dominant component for both components.

Example 1: Calculate the maximum likely dose to an individual exposed to a patient who has received 2,220 megabecquerels (MBq) (60 millicuries (mCi)) of I-131. The patient has been given instructions to maintain a prudent distance from others for at least 2 days, lives alone, drives home alone, and stays at home for several days without visitors.

RG-8.39, Rev. 1, Appendix B, Page B-7

Solution: Use Equation B-1 to calculate the dose to total decay (t = ) based on the physical half-life.

(This calculation illustrates the use of physical half-life. To account for biological elimination, use the calculations described in the next section.)

34.6

() =

r2 Because the patient was given instructions on how to reduce exposure as recommended for an occupancy factor of E = 0.125, the occupancy factor of 0.125 at 1 meter may be used.

2 34.6 2.2 (8.04)(0.125)

() =

(100 cm)2

() = 4.59 (0.459 )

Because the dose is less than 5 mSv (0.5 rem), the patient may be released; however, 10 CFR 35.75(b) requires the licensee to instruct the patient on how to maintain doses to others as low as is reasonably achievable. The licensee must maintain a record of the calculation in accordance with 10 CFR 35.2075(a) because it used an occupancy factor less than 0.25 at 1 meter.

B-2. Effective Half-Life A licensee may account for the effective half-life of the radioactive material to demonstrate compliance with the dose limits for individuals exposed to the patient that are stated in 10 CFR 35.75, Release of Individuals Containing Unsealed Byproduct Material or Implants Containing Byproduct Material. The effective half-life is defined as follows:

= +

(Equation B-2)

Where Tb = biological half-life of the radionuclide Tp = physical half-life of the radionuclide The behavior of disassociated I-131can be modeled using two components: (1) extrathyroidal iodide (i.e., existing outside of the thyroid) and (2) thyroidal iodide following uptake by the thyroid.

The effective half-lives for the extrathyroidal and thyroidal fractions (F1 and F2, respectively) can be calculated with the following equations:

1 1 = (Equation B-3) 1 +

2 2 = 2 +

(Equation B-4) where Tb1 = biological half-life for extrathyroidal iodide Tb2 = biological half-life of iodide following uptake by the thyroid Tp = physical half-life of I-131 However, simple exponential excretion models do not account for (1) the time for the I-131 to be absorbed from the stomach to the blood and (2) the holdup of iodine in the urine while in the bladder.

RG-8.39, Rev. 1, Appendix B, Page B-8

Failure to account for these factors could result in an underestimate of the dose to another individual.

Therefore, this guide makes a conservative approximation to account for these factors by assuming that, during the first 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months after the administration, about 80 percent of the I-131 administered is removed from the body at a rate determined only by the physical half-life of I-131.

Thus, an equation to calculate the dose from a patient administered I-131 may have three components. The first component is the dose for the first 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months (0.33 day) after administration. This component comes directly from Equation B-1 using the physical half-life and a factor of 80 percent. The second component is the dose from the extrathyroidal component from 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months to total decay. In this component, the first exponential factor represents the activity at t = 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months based on the physical half-life of I-131. The second exponential factor represents the activity from t = 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months to total decay based on the effective half-life of the extrathyroidal component. The third component, the dose from the thyroidal component for 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months to total decay, is calculated in the same manner as the second component.

Equation B-5 shows the full equation.

0.693(0.33) 34.6 1 (0.8) 1

+

() = (Equation B-5)

(100 cm)2 0.693(0.33)/ 0.693(0.33)/

2 1 1 + 2 2 2 where F1 = extrathyroidal uptake fraction F2 = thyroidal uptake fraction El = occupancy factor for the first 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months E2 = occupancy factor from 8 hours9.259259e-5 days 0.00222 hours 1.322751e-5 weeks 3.044e-6 months to total decay Equations B-1, B-3, and B-4 define all the other parameters. Table B-1 lists acceptable values for F1, T1eff, F2, and T2eff for thyroid ablation and treatment of thyroid remnants after surgical removal of the thyroid for thyroid cancer. If these values have been measured for a specific individual, the measured values may be used.

Staff Regulatory Guidance Position 3.1 in this regulatory guide describes the record of the patients release as required by 10 CFR 35.2075(a).

Example 2, Thyroid Cancer: Calculate the maximum likely dose to an individual exposed to a patient who has been administered 7,400 MBq (200 mCi) of I-131 for the treatment of thyroid remnants and metastases.

Solution: In this example, calculate the dose using Equation B-5 to account for the elimination of I-131 from the body based on the effective half-lives appropriate for thyroid cancer. The physical half-life and the exposure rate constant are from Table A-1 in Appendix A to this document. The uptake fractions and effective half-lives are from Table B-1. An occupancy factor, E, of 0.75 at 1 meter will be used for the first component because the time period under consideration is less than 1 day. However, for the second and third components, an occupancy factor of 0.25 will be used because (1) the effective half-life associated with the dominant component is greater than 1 day and (2) the patient was asked patient-specific questions to justify the occupancy factor (see Section B.1.2 of this appendix).

RG-8.39, Rev. 1, Appendix B, Page B-9

Table B-1. Uptake Fractions and Effective Half-Lives for I-131 Treatments MEDICAL EXTRATHYROIDAL COMPONENT THYROIDAL COMPONENT CONDITION Uptake Fraction Effective Half-Life Uptake Fraction Effective Half-Life F1 T1eff (day) F2 T2eff (day)

Hyperthyroidism 0.20a 0.32b 0.80a 5.2a Postthyroidectomy 0.95c 0.32b 0.05c 7.3b for Thyroid Cancer

a. See M.G. Stabin, C.S. Marcus, E.E. Watson, and R.D. Salk, Radiation Dosimetry for the Adult Female and Fetus from Iodine-131 Administration in Hyperthyroidism, Journal of Nuclear Medicine, 32(5):808-813, issued June 1991. The thyroid uptake fraction of 0.80 was selected as one that is seldom exceeded by the data shown in Figure 1 in this cited document. The effective half-life of 5.2 days for the thyroidal component was derived from a biological half-life of 15 days, which was obtained from a straight line fit that accounts for about 75 percent of the data points shown in Figure 1 of this cited document (Ref. B-7).

b. See International Commission on Radiological Protection (ICRP) No. 53, Radiation Dose to Patients from Radiopharmaceuticals, issued March 1987. The data in this ICRP document suggest that the extrathyroidal component effective half-life in normal subjects is about 0.32 days. If other data are lacking, apply this value to hyperthyroid and thyroid cancer patients. For thyroid cancer, ICPR No. 53 suggests that the thyroidal component effective half-life of 7.3 days is based on a biological half-life of 80 days (adult thyroid) (Ref. B-8).

c. Dr. M. Pollycove, M.D., a U.S. Nuclear Regulatory Commission (NRC) medical visiting fellow, recommended the thyroidal uptake fraction of 0.05 as an upper limit postthyroidectomy for thyroid cancer.

Substituting the appropriate values into Equation B-5, the dose to total decay is as follows:

34.6 (2.2)(200) 0.693(0.33) 0.693(0.33)

() = 2 (0.75)(8.04)(0.8) 1 8.04 + 8.04 (0.25)(0.95)(0.32)

(100 cm) 0.693(0.33)

+ 8.04 (0.25)(0.05)(7.3)

D() = 4.53 mSv (0.453 rem)

Therefore, thyroid cancer patients administered 7,400 MBq (200 mCi) of I-131 or less would not have to remain under licensee control and could be released under 10 CFR 35.75, assuming that the foregoing assumptions can be justified for the individual patients case and that the patient is given instructions. Patients administered somewhat larger activities could also be released immediately if the dose to another individual is not likely to be greater than 5 mSv (0.5 rem).

In the example above, the thyroidal fraction, F2 = 0.05, is a conservative assumption for persons who have had surgery to remove thyroidal tissue. If F2 has been measured for a specific patient, the measured value may be used.

Example 3, Hyperthyroidism: Calculate the maximum likely dose to an individual exposed to a patient who has been administered 2,035 MBq (55 mCi) of I-131 for the treatment of hyperthyroidism (i.e., thyroid ablation).

Solution: In this example, calculate the dose using Equation B-5, Table A-1, and Table B-1 to account for the elimination of I-131 from the body by using the effective half-lives appropriate for hyperthyroidism.

Use an occupancy factor, E, of 0.25 at 1 meter for the second and third components of the equation because patient-specific instructions were provided to justify the occupancy factor (see Section B.1.2 of this appendix).

RG-8.39, Rev. 1, Appendix B, Page B-10

Substituting the appropriate values into Equation B-5, the dose to total decay is as follows:

0.693(0.33) 34.6 (2.2)(55) (0.75)(8.04)(0.8) 1 8.04

() =

(100 cm)2 0.693(0.33) 0.693(0.33)

+ 8.04 (0.25)(0.20)(0.32) +

8.04 (0.25)(0.80)(5.2)

D() = 4.86mSv (0.486 rem)

Therefore, hyperthyroid patients administered 2,035 MBq (55 mCi) of I-131 would not have to remain under the control of the licensee and could be released under 10 CFR 35.75 when the occupancy factor of 0.25 in the second and third components of the equation is justified.

In the example above, the thyroidal fraction, F2 = 0.8, is a conservative assumption for persons who have this treatment for hyperthyroidism. If F2 has been measured for a specific patient, the measured value may be used.

B-3. Internal Dose For some radionuclides, such as I-131, the concern is that the internal dose of an individual from exposure to a released patient could be significant. Equation B-6 can be used to calculate a rough estimate of the maximum likely committed effective dose equivalent from internal exposure.

Di = Q (10-5) (DCF) (Equation B-6) where Di = maximum likely internal committed effective dose equivalent to the individual exposed to the patient in rem Q = activity administered to the patient in millicuries 1x10-5 = assumed fractional intake DCF = dose conversion factor used to convert an intake in millicuries to an internal committed effective dose equivalent (such as tabulated in Ref. B-2)

Equation B-6 uses a value of 1x10-5 as the fraction of the activity administered to the patient that would be taken in by the individual exposed to the patient. A common rule of thumb is to assume that no more than 1 millionth of the activity being handled will become an intake to an individual working with the material. This rule of thumb was developed in Reference B-3 for cases of worker intakes during normal workplace operations, worker intakes from accidental exposures, and public intakes from accidental airborne releases from a facility; however, it does not specifically apply to cases of intake by an individual exposed to a patient. However, two studies (Refs. B-4 and B-5) of the intakes of individuals exposed to patients administered I-131 indicated that intakes were generally of the order of 1 millionth of the dosage administered to the patient and that internal doses were far below external doses. To account for the most highly exposed individual and to add a degree of conservatism to the calculations, a fractional transfer of 1x10-5 has been assumed.

Example 4, Internal Dose: Using the ingestion pathway, calculate the maximum internal dose to a person exposed to a patient who has been administered 1,110 MBq (33 mCi) of I-131. The ingestion RG-8.39, Rev. 1, Appendix B, Page B-11

pathway was selected because most of the intake would likely be through the mouth or through the skin, which is most closely approximated by the ingestion pathway.

Solution: Use Equation B-6 for the solution to this example. The DCF for the ingestion pathway is 53 rem/mCi from Table 2.2 of Reference B-2.

Substituting the appropriate values into Equation B-6, the maximum internal dose to the person is as follows:

Di = (33 mCi) (10-5) (53 rem/mCi) Di = 0.17 mSv (0.017 rem)

In this case, the external dose to the other person would be no greater than 5 mSv (0.5 rem),

whereas the internal dose would be about 0.17 mSv (0.017 rem). Thus, the internal dose is about 3 percent of the external gamma dose. Internal doses may be ignored in the calculations if they are likely to be less than 10 percent of the external dose because the internal dose would be significantly less than the uncertainty in the external dose.

The National Council on Radiation Protection and Measurements (NCRP) also concluded that internal contamination is relatively unimportant in the case of patient release. NCRP addressed the risk of intake of radionuclides from a patients secretions and excreta in NCRP Commentary No. 11, Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients, dated February 28, 1995 (Ref. B-6). NCRP concluded that a contamination incident that could lead to a significant intake of radioactive material is very unlikely. NUREG-1492 further discusses the subject.

RG-8.39, Rev. 1, Appendix B, Page B-12

REFERENCES FOR APPENDIX B 7 B-1. U.S. Nuclear Regulatory Commission, NUREG-1492, Regulatory Analysis on Criteria for the Release of Patients Administered Radioactive Material, Washington, DC, February 1997.

B-2. Eckerman, K.F., A.B. Wolbarst, and A.C.B. Richardson, Federal Guidance Report No. 11:

Limiting Values of Radionuclide Intake and Air Concentration and Dose Conversion Factors for Inhalation, Submersion, and Ingestion, U.S. Environmental Protection Agency, Washington, DC, September 1988.

B-3. Brodsky, A., Resuspension Factors and Probabilities of Intake of Material in Process (or Is 10-6 a Magic Number in Health Physics?), Health Physics, 39(6):992-1000, January 1981.

B-4. Buchanan, R.C.T., and J.M. Brindle, Radioiodine Therapy to Out-patientsThe Contamination Hazard, British Journal of Radiology, 44(523):557, August 1971.

B-5. Jacobson, A.P., P.A. Plato, and D. Toeroek, Contamination of the Home Environment by Patients Treated with Iodine-131, American Journal of Public Health, 68(3):225-230, March 1978.

B-6. National Council on Radiation Protection and Measurements Commentary No. 11, Dose Limits for Individuals Who Receive Exposure from Radionuclide Therapy Patients, Bethesda, MD, February 28, 1995.

B-7. M.G. Stabin, C.S. Marcus, E.E. Watson, and R.D. Salk, Radiation Dosimetry for the Adult Female and Fetus from Iodine-131 Administration in Hyperthyroidism, Journal of Nuclear Medicine, 32(5):808-813, issued June 1991.

B-8. International Commission on Radiological Protection (ICRP) No. 53, Radiation Dose to Patients from Radiopharmaceuticals, issued March 1987.

7 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. 1, Appendix B, Page B-13

ML20056E123

Text

Background

Background

Navigation menu

Search