ML19094A626

M190404: Scheduling Note and Slides - Meeting with the Advisory Committee on the Medical Uses of Isotopes (Public Meeting)

ML19094A626
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Issue date:	04/04/2019
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M190404
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SCHEDULING NOTE Title: MEETING WITH THE ADVISORY COMMITTEE ON THE MEDICAL USES*OF ISOTOPES (Public Meeting)

Purpose: Provide an opportunity to hear views from the Advisory Committee on the Medical Uses of Isotopes (ACMUI) on medical-related topics of regulatory interest.

Scheduled: April 4, 2019 10:00 am I

Duration: Approx. 2 hours2.314815e-5 days <br />5.555556e-4 hours <br />3.306878e-6 weeks <br />7.61e-7 months <br /> Location: Commissioners' Conference Room, 1st fl OWFN I

Participants: Presentation ACMUI Panel 50 mins.* I Christopher J. Palestro, M.D., ACMUI Chair I Topic:

• Overview of ACMUI Activities I Darlene F. Metter, M.D., ACMUI Vice Chair Topics:

• ACMUl's Comments on the Guidelines to Nursing Mothers for Exposure from the Medical Administration of Radioactive Materials (Nursing Mother Guidelines)

• ACMUl's Comments on the Training and Experience Requirements for All Modalities (35.300 Uses)

Ronald D. Ennis, M.D., ACMUI Radiation Oncologist (Brachytherapy)

Topic:

• ACMUl's Review and Analysis of Reported Medical Events from Fiscal Years 2014-2017 Laura Weil, ACMUI Patients' Rights Advocate Topic:

• Patients' Rights Advocate's Perspective on:

• Nursing Mother Guidelines

• The Training and Experience Requirements for All Modalities (35.300 Uses)

• Medical Event Reporting

Commissioners' Q & A 50 mins.

Discussion - Wrap-up 5mins.

• For presentation only and does not include time for Commission Q & A's

. "

U.S.NRC United States Nuclear Regulatory Commission Protecting People and the Environment ACMUI Activities: Overview Christopher J. Palestro, M.D.

ACMUI Chairman April 4, 2019 1

, ,,

Overview of the ACMUI

• Role

• Membership

• Topics

• Future 2

ACMUl's Role

• Provide advice on policy and technical issues that arise in regulating medical use of radioactive material for diagnosis and the.rapy

• Comment on changes to NRC regulations and guidance

• Evaluate certain non-routine uses of radioactive material

• Provide technical assistance

• Bring key issues to the attention of the Commission for appropriate action.

3

ACMUI Membership (13 members)

• Healthcare administrator (Dr. Arthur Schleipman)

• Nuclear medicine physician (Dr. Christopher Palestro)

• 2 Radiation oncologists (Dr. Ronald Ennis &

Dr. Harvey Wolkov*)

• Nuclear cardiologist (Dr. Vasken Dilsizian)

• Diagnostic radiologist (Dr. Darlene Metter)

• pending clearance 4

ACMUI Membership (13 members)

• 2 Medical physicists Nuclear medicine (Ms. Melissa Martin)

Radiation therapy (Mr. Zoubir Ouhib)

• Nuclear pharmacist (Mr. Richard Green)

• Radiation safety officer (Mr. Michael Sheetz)

• Patients' rights advocate (Ms. Laura Weil)

• FDA representative (Dr. Michael O'Hara)

• Agreement states representative (Ms. Megan Shober) 5

ACMUI Topics (2018-2019)

• Analysis of medical events

• ABS medical event case study program

• Non-medical events

• Training & experience for all modalities

• . Draft revision of Leksell Gamma Knife Perfexion &

Icon

• Compounding sterile/non-sterile radiopha rmaceutica Is 6

ACMUI Topics (2018-2019)

• Nursing mothers' guidelines

• ACMUI Bylaws

• Appropriateness of medical event reporting

• Yttrium-90 Microspheres Brachytherapy Licensing

• ACMUI external communications 7

ACMUI Topics (2018-2019)

Staff Presentations

• T & E stakeholder outreach plan

• ACMUI Reporting Structure

• Medical Related Events

• Summary of Changes to 10 CFR Part 35

• Yttrium-90 Microspheres Brachytherapy *Licensing Guidance

• Medical Team Highlights

• How ACMUI, Subcommittees, NRC Staff &

Management work together under FACA 8

Future

• ACMUI will continue to

- Provide advice and technical assistance

- Comment on NRC regulations and guidance

- Evaluate uses of radioactive material

- Bring key issues to the attention of the Commission 9

Rest of Today's Agenda

• . Darlene F. Metter, M.D. (ACMUI Vice Chair)

-Comments on the Guidelines to Nursing Mothers for Exposure from the Medical Administration of Radioactive Materials

-Comments on T & E Requirements for All Modalities (35.300 Uses)

• Ronald D. Ennis, M.D. (ACMUI Radiation Oncologist Brachytherapy)

-Review and Analysis of Reported Medical Events for FY's 2014-2017 10

Rest of Today's Agenda (cont'd)

• Laura Weil (ACMUI Patients' Rights Advocate)

-Perspective on:

Nursing Mother Guidelines T & E Requirements for All Modalities (35.300 Uses)

Medical Event Reporting 11

Acronyms

• ABS: American Brachytherapy Society

• ACMUI: Advisory Committee on Medical Uses of Isotopes

• FDA: Food and Drug Administration

• FY: Fisca I Year

• T&E: Training and Experience 12

. .

7 U.S.NRC U n ited States N uclear Regulatory C omm issi on Protecting People and the Environment Comments on the Guidelines to Nursing Mothers for Exposure from the Medical Administration of Radioactive Materials Darlene F. Metter, M.D.

ACMUI Vice Chairman A ril4, 20 19 13

Subcommittee Members

• Vasken Dilsizian, M.D.

• Darlene Metter, M.D. (Chair)

• Christopher Palestro, M.D.

• Pat Zanzonico, Ph.D. (previous member) 14

Nursing Mother Guidelines Charge: "Review the radiation exposure from diagnostic and therapeutic radiopharmaceuticals, including brachyth.erapy, to the nursing mother and child."

15

Patient Release

• Patient release (nursing mother): Total EDE to the nursing child is< 5 mSv.

• If exposure could exceed 1 mSv to the nursing child, written instructions of adverse consequences must be given if nursing is not stopped & guidance on .t he discontinuation of breast feeding. {10 CFR 35.75) 16

Radiopharmaceuticals (RP) in Breast Milk

• Most nursing mothers administered RP require a temporary cessation of breast feeding.

• A few _

nursing mothers administered RP may require complete cessation of breast feeding.

17

Radiopharmaceuticals (RP) in Breast Milk

• Exception: (to decrease the breast dose)

• 131 1-Nal dose to the lactating breast

- 131 1-Nal 150 mCi = 200 R (breast)

• _

To decrease the breast dose, lactation must cease. Thus, breastfeeding must stop 6 weeks prior to RP administration and for that child. May breastfeed for future children.

18

Radiation Exposure During Nursing

• Mother: Internal

• Child: External & Internal 19

Radiation Exposure: Nursing Child -

External

• Mother is a significant radiation source, especially during routine child care.

• ALARA:

• Time: increased

• Distance: decreased 20

-~-- ----

Radiation Exposure: Nursing Child -

Internal

• Ingested radioactive breast milk

• Depends on the RP ("'0.3-5% in milk) 131

• 1-Nal: Cease breast feeding* 6 weeks before administration and for the current child.

• May breast feed for future children.

21

- - -

Nursing Mother Recommendations

• Nursing interruption

• Radiopharmaceutical

• Stop

• 131 1-Nal* 124 I 1-Nal all alpha I I 177 Lu dotatate diagnostic or therapeutic

• None

• 1 hour1.157407e-5 days <br />2.777778e-4 hours <br />1.653439e-6 weeks <br />3.805e-7 months <br />

• 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br />

• Stop breast feeding 6 weeks prior to therapy 22

Nursing Mother Recommendations (Continued)

• Nursing interruption

• Radiopharmaceutical

• 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br />

• 99mTc

• 3 days

• 123 1-Nal I

• 4 days

• 201 Tl-chloride

• 6 days

• 111 1n-WBC, - pentetreotide

• 28 days

• 67Ga s9zr I

23

Sealed Sources

• Y-90 Microspheres: No interruption

• Breast & sentinel lymph node sources: No interruption as long as source(s) is(are) not in the nursing mother 24

Nuclear Medicine Department Signage

• Inform nursing mothers or mothers planning to nurse in the near future who are scheduled for a NM procedure, that certain RP may require radiation safety precautions.

• Such patients are advised to notify the NM staff or physician prior to their procedure.

25

• Subcommittee Report

• February 1, 2018 public teleconference ACMUI unanimously approved the submitted report with some caveats (e.g., calculations, modifications to tables).

• September 20, 2018 ACMUI Fall Meeting ACMUI unanimously approved the revised report with additional language regarding FDA-approved RP and the need to evaluate RPs not encompassed in the report.

26

Acronyms

• ACMUI -Advisory Committee on the Medical Uses of Isotopes

• ALARA ~ As Low As(ls) Reasonably Achievable

• CFR - Code of Federal Regulations

• EDE - Effective Dose Equivalent

• NRC - Nuclear Regulatory Commission

• R- Rad

• RP - Radiopharmaceuticals 27

U.S.NRC United States Nuclear Regulatory Commission Protecting People and the Environment Comments on Training & Experience Requirements for All Modalities {35.300 Uses)

Darlene *F. Metter, M.D.

ACMUI Vice Chairman April 4, 2019 28

Subcommittee Members

• Ronald Ennis, M.D.

• Darlene Metter, M.D. (Chair)

• A. Robert Schleipman, Ph.D.

• Michael Sheetz, M.S.

• Megan Shober, M.S.

• Laura Weil, M.S.

29

- - - - - - - - - - - - ~

March 2018 Subcommittee Recommendation

• No current AU shortage.

• Reconsider an alternate AU p*a thway under 10 CFR 35.390

• Rationale: 2 recent events

- 1/2018 FDA approved 177 Lu dotatate* with a potential for greater use

- Decrease in number of 1st time candidates sitting for the American Board of Nuclear Medicine exam 30

Potential AU Shortage 31

10 CFR 35.390 AU Pathways

• Pathway 1: Board Certification*

- Nuclear Medicine -(NM)

- Radiation Oncology (RO)

• American Boards of Nuclear Medicine, Radiology &

Osteopathic Radiology 32

10 CFR 35.390 AU Pathways *

• Pathway 2: Alternate Pathway

• 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of T&E includes 200 lab hours in basic radionuclide handling techniques in the medical uses of unsealed byproduct material requiring a WD

• Diag Radiology, redesigned* (rDR)

• Nuclear Radiology (N R)

• 16 months NM in a 48 month Diagnostic Radiology program 33

2018-2019 for Pathways 1 & 2

• In-Training * ,VGraduates/'{ear

• NM: 79

• NM: 50

• NR: 11

• NR: 11

• rDR: 56

• rDR: 14

• RO: 775

• RO: 194 Total: 921 Total: 269 34

AU Shortage?

• 2018-19 AU 35.390 pipeline: 921 *

• 2019 Graduates: 269*

• 2018 ABNM:_3,591 practicing AU

• 2019: No AU shortage

• Graduate totals include Pathway 1 & 2 35

Limited-Scope AU 36

. .

Radionuclide Therapy. .

• Radionuclide{RN) therapy: highest risk &

highest impact of all NM procedures.

• To protect public health & safety, AUs must have a basic level of T&E.

• Limited-scope & full AUs must have equivalent level of procedural competency.

37

• --

' .

Limited- Scope AU

• Basic knowledge topics: § 35.390

• Due to complexity & overlap of these topics, any category would include nearly all of§ 35.390

Conclusion:

Subcommittee does not recommend a limited-scope AU pathway 38

1--,

Final ACMUI Recommendations 39

Final Recommendations

• The Committee strongly supports the current AU pathways for§ 35.390, which protects the public's health & safety.

• There is no objective data to support an AU

~hortage.

40

Final Recommendations

• The Committee does not recommend a limited-scope AU pathway for unsealed byproduct material for which_a written directive is required.

41 L

. '

Final Recommendations

• The Committee unanimously agrees that if the NRC pursues a limited-scope AU pathway, the AU candidate must attest to the acquisition of§ 35.390 knowledge topics &

skills by successfully completing a formal competency assessment with continued formal periodic competency reassessment to maintain his/her limited-scope AU status.

42

Subcommittee Report

• February 26, 2019

• ACMUI approved the report and *its recommendations (11 Y/lN) with one revision to add the language below:

-Subcommittee will work with the NRC staff to develop an AU curriculum of knowledge topics.

43

Acronyms

• ABNM - American Board of Nuclear Medicine

• ABR - American Board of *Radiology

• ACMUI -Advisory Committee on the Medical Uses of Isotopes

• AU - Authorized User

• CFR - Code of Federal Regulations

• FDA *- U. S. Food and Drug Administration

• 177 Lu - 177 Lutetium

• NM - Nuclear Medicine 44

Acronyms

• NR - Nuclear Radiology

• NRC - Nuclear Regulatory Commission

• R- Rad

• RN - Radionuclide

• RO - Radiation Oncology

• RP - Rad_iopharmaceutical

• rDR- redesigned Diagnostic Radiology pathway

• T&E - Training and Exp*erience

• WD - Written Directive 45

U.S.NRC United States Nuclear Regulatory Commission Protecting People and the Environment ACMUl's Review and Analysis of Reported Medical Events from FVs 2014-2017 Ronald D. Ennis, M.D.

ACMUI Radiation Oncologist A~ril 4, 2019 46

Subcommittee Members

• Ronald D. Ennis, M.D. (Chair)

• Richard Green

• Darlene Metter, M.D.

• Michael O'Hara, Ph.D.

• John Suh, M.D. former member

• Michael Sheetz 47

Subcommittee Objective

• To discern common themes within each section of 10 CFR Part 35 and across the sections, to inform a discussion of possible ways to decrease MEs.

• The subcommittee reviewed the last three reports of this subcommittee {FYs 2014-16) as well as the staff's spring report for FY 2017.

48

Probable ME Themes

• Two overarching themes emerged

- Performance of a time out immediately prior to administration of radioactive byproduct material, as is done in surgery and other settings, could have prevented some MEs

- Lack of recent or frequent performance of the specific administration appears to be a contributing factor in a number of cases 49

35.200 Use of Unsealed Byproduct Material for Imaging and Localization Medical Events Summary Cause Wrong drug* 0 3 3 0 6 Wrong dosage 5 0 3 3 11 Wrong patient 1 1 2 0 4 6 4 3 21

• Inmost cases wrong drug was also wrong dosage 21 events over 4 years 50

35.200 Use of Unsealed Byproduct Material for Imaging and Localization How Can These Events Be Prevented?

• Wrong drug: Time out - confirm the order, compare to the prescription

• Wrong dosage: If a dose calibrator is available - measure the activity

• Wrong patient: Time out - Verify patients by two means of identification

• 10/21 preventable if time out had been used 51

35.400 Manual Brachytherapy Medical Event Summary Applicator issue (e.g. 1 movement during implant Wrong site implanted (e.g. 3 1 1 1 6 penile bulb)

Activity/prescription error 1 2 0 1 4 (e.g. air kerma vs mCi)

Prostate Dose 0 4 18 5 27 52

I *

.

35.400 Manual Brachytherapy Medical Event Summary Total ME 8 7 40 "Time out" may have 1 2 0 1 4 prevented (10%)

Lack of experience may 3 1 1 1 6 have played a role (15%)

53

.

35.400 Manual Brachytherapy

• Many MEs in this category are no longer categorized as MEs due to change from dose- to activity-based definition.

• Lack of experience possibly plays a role in the true MEs of this type, but hard to assess to what degree in each case.

11

• In approximately 25% of cases, a "time out or enhanced retraining prior to performance of an uncommon procedure might have prevented the ME.

54

35.600 Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic unit Medical Event Summary Wrong position 3 6 1 2 Wrong reference length 2 3 0 2 Wrong plan 1 3 1 0 Wrong dose/source strength 2 0 0 0 Machine malfunction . 2 2 3 2 Software fa i Iu re -0 -0 -0 2 (9 pts)

Total [37 events over 4 years] 10 14 . 5 8 (14 pts) 55

35.600 Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic unit Medical Event Summar Location Breast 1 1 0 0 Gynecological 5 9 2 7 (14 pts)

Skin 2 1 1 0 Bronchus 1 2 0 0 Prostate 0 0 2 0 Brain -1 -0 1 Total 10 14 5 8 (14 pts)

GYN tumors most common site of ME 56

I -

35.600 Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic unit MEs that may have ~een prevented by "timeout" (wrong plans or dose)

• 2014 3/10 events

• 2015 3/14 events

• 2016 1/5 events

• 2017 0/8 events Total 6/37 {16.2%)

57

. -

35.600 Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic unit MEs caused by "infrequent user"

• This is difficult to determine based on information on NMED. If assumption is made about wrong position as surrogate for #infrequent" user

• 2014 3/10 events

• 2015 6/14 events

• 2016 1/5 events

• 2017 .2/8 events

• Total 12/37 (32.4%)

58

35.1000 Radioactive Seed Localization Medical Event Summary Total Medical Events Cause:

Delayed seed removal (patient 1 1 intervention)

Lost seed 1 Wrong implant site 1 59

35.1000 Leksell Gamma Knife Perfexion TM and Leksell Gamma Knife Icon TM Medical Event Summary Total Medical Events 8 Cause:

Patient positioning system 8 misalignment by vendor (same site)

Patient setup error 2 Patient movement . 1 Wrong site (treatment plan) 1 60

35.1000 V-90 Theraspheres

. Medical Event Summary Total Medical Events 13 15 Cause:

> 20% residual activity remaining in 6 9 7 delivery device Delivery device setup error 1 2 Wrong dose (treatment plan calculation 1 1 4 error)

Wrong site (catheter placement error) 1 1. 2 2 Wrong site (shunting) 1 61

35.1000 Y-90 SirSpheres Medical Event Summary Total Medical Events 8 Cause:

> 20% residual activity remaining in 10 2 9 7 delivery device not due to stasis Wrong site (shunting) 2 4 Delivery device setup error 1 3 Wrong dose (treatment plan calculation 1 1 2 error)

Wrong site (catheter placement error) 1 2 1 62

Actions to Prevent 35.1000 Y-90 Microsphere MEs Cause

• Review mechanics of Y-90 microsphere delivery -device and setup procedures

• Confirm all data and calculations i 62% treatment plan 11

• Perform Time Out" to assure all elements of treatment are in

>20% residual activity (not due to stasis) *d . hW . D. .

accor a*nce wit r1tten 1rect1ve Wro g dose ( rea m nt pla calculation error)

Wro g si (incor ect cathet r placement) 1 Wrong site (shunting)

Delivery device setup error 63

~

1 I 35.1000 MEs That May Have Been Prevented by

Time Out

2014 2015 0/1 0/8 2/18 2016 0/1 2/3 3/26 2017 0 0 3/23 Total 1/4 {25%) 3/12 {25%) 11/91 {12%}

64

. '

35.1000 MEs That May Have Been Attributed to Lack of Experience or Infrequent User 0/2 1/24 2015 0/1 0/8 3/18 0/1 2/3 1/26 2017 0 0 2/23 Total 0/4 (0%} 2/12 (17%) 7/91 (8%}

65

--

Possible Elements of a Time Out-

• Identity of patient via two

• Others as applicable identifiers (e.g. name and - units of activity (LDR DOB) prostate)

• Procedure to be performed - anatomic location

• Isotope - patient name on treatment plan

• Activity

. - treatment plan

• Dosage independent second check has been performed

• - reference length (HDR)

- Implant site location (RSL) 66

---

• Possible Elements of Refresher for Infrequent Procedure

• Take review course from professional society

• Read review articles

• Speak to colleague with experience

• Do dry run of procedure with the team

• Review mechanics of device set up and procedure 67

• I

• Recommendation for Action At the September 2018 ACMUI Meeting, the ACMUI recommended the NRC issue an Information Notice alerting AUs to the themes identified herein.

The NRC staff accepted this recommendation/

pending resource availability 68

. - ' .

Acronyms

• .10 CFR - Title 10 of the Code of Fede.r al Regulations

• ABS - American Brachytherapy Society

• ACMUI -Advisory Committee on the Medical Uses of Isotopes

• AUs - authorized users

• DOB - date of birth

• FDA: Food and Drug Administration

• FY - Fiscal Year

• Gy- Gray 69

• .. p

• Acronyms

• gyn - gynecological

• HDR - high dose-rate

• LDR - low dose rate

• mCi - milliCurie

• ME - Medical Event

• RSL - radioactive seed localization

• T&E - training and experience

• Y .;,_Yttrium 70

l U.S.NRC United States Nuclear Regulatory Commission Protecting People and the Environment Patients' Rights Advocates' Perspectives Laura M. Weil ACMUI Patients' Rights Advocate April 4, 2019 71

Topics

- Nursing Mother Guidelines

- The Training and Experience Requirements for All Modalities

[Title 10 Code of Federal Regulation 35.300 Uses]

- Medical Event Reporting 72