ML20258A241
ML20258A241 | |
Person / Time | |
---|---|
Issue date: | 09/14/2020 |
From: | Office of Nuclear Material Safety and Safeguards |
To: | |
Jamerson K | |
References | |
Download: ML20258A241 (70) | |
Text
1 MEETING AGENDA ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES September 21-22, 2020 WEBEX NOTE: Sessions of the meeting may be closed pursuant to 5 U.S.C. 552(b) to discuss organizational and personnel matters that relate solely to internal personnel rules and practices of the ACMUI; information the release of which would constitute a clearly unwarranted invasion of personal privacy; information the premature disclosure of which would be likely to significantly frustrate implementation of a proposed agency action; and disclosure of information which would risk circumvention of an agency regulation or statute.
Monday, September 21, 2020 OPEN SESSION
- 1. Opening Remarks Mr. Einberg will formally open the meeting and provide opening remarks.
C. Einberg, NRC 10:00 - 11:30
- 2. Old Business Ms. Jamerson will review past ACMUI actions and recommendations and provide NRC responses.
- 3. Open Forum The ACMUI will identify medical topics of interest for further discussion.
K. Jamerson, NRC ACMUI
- 4. Medical Events Subcommittee Report Dr. Ennis will provide an analysis of FY19 medical events.
R. Ennis, ACMUI 11:30 - 12:15 BREAK/LUNCH
- 5. Non-Medical Events Mr. Sheetz will provide an analysis of FY19 non-medical events reported by medical use facilities and commercial pharmacies.
M. Sheetz, ACMUI 12:15 - 2:00
- 6. New Drug Development and Labeling Mr. Lutterodt will discuss the U.S. Food and Drug Administrations regulatory process for new drug development and labeling.
F. Lutterodt, FDA
- 7. Dosimetry Methodology Update for Regulatory Guide 8.39, Phase 2 Revision Dr. Hamby will discuss the dosimetry methodology update for the Regulatory Guide 8.39, Phase 2 revision.
D. Hamby, RCD Radiation Protection Assoc.
2:00 ADJOURN FOR THE DAY Tuesday, September 22, 2020 CLOSED SESSION 10:00 - 12:00
- 8. INFOSEC Training
- 9. Ethics Training
- 10. Allegations Training R. Norman, NRC C. Safford, NRC S. Hawkins, NRC
2 12:00 - 12:15 BREAK Tuesday, September 22, 2020 OPEN SESSION
- 11. Medical Team Updates Ms. Dimmick will provide an update on Medical Radiation Safety Team activities.
L. Dimmick, NRC 12:15 - 1:45
- 12. Open Forum The ACMUI will discuss medical topics of interest previously identified.
- 13. Administrative Closing Ms. Jamerson will provide a meeting summary and propose dates for the spring 2021 meeting.
K. Jamerson, NRC 1:45 ADJOURN
2019 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE Target Completion Date for NRC Action 17 The ACMUI endorsed the Appropriateness of Medical Event Reporting Subcommittee report and the recommendations provided therein.
9/10/2019 ACMUI Action Open Spring 2021 18 The ACMUI endorsed the Evaluation of Extravasations Subcommittee Report, as amended, to note that under future revisions to Part 35 rulemakings, extravasations be captured as a type of passive patient intervention in the definition of patient intervention.
9/10/2019 ACMUI Action Open Spring 2021 20 The ACMUI endorsed the Institutional Memory Subcommittee Report, as amended, to include the recommendation that a complete list of ACMUI members be updated and added to the webpage. The Subcommittee membership was amended to add Dr. Wolkov.
9/11/2019 ACMUI Action Open*
09/14/2020 STATUS
- Action completed via the September 14, 2020 NRC Response Memorandum (ADAMS Accession No. ML20254A179) -
pending formal closure by the ACMUI at the fall 2020 meeting.
1
2020 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE Target Completion Date for NRC Action 1
The ACMUI endorsed the Regulatory Guide (RG) 8.39, "Release of Patients Administered Radioactive Material" Subcommittee report and the recommendations provided therein regarding the draft final RG 8.39, Revision 1, Phase 1.
3/11/2020 Accepted Open*
09/14/2020 2
Dr. Metter formed a subcommittee to review the impacts that COVID-19 could have or is having on the medical use community and determine if potential impacts could help the NRC prepare for any regulatory impacts. Subcommittee membership includes: Dr. Vasken Dilsizian, Mr. Richard Green, Dr. Hossein Jadvar (chair), Ms. Melissa Martin, Ms. Megan Shober, and Dr. Harvey Wolkov. Non-voting subcommittee consultants include: Mr. Gary Bloom and Mr. Zoubir Ouhib.
NRC staff resource: Ms. Lisa Dimmick 03/30/2020 Accepted Open*
09/14/2020 3
Dr. Metter amended the membership of the Training and Experience Requirements Subcommittee. Subcommittee membership now includes: Dr. Ronald Ennis, Dr. Hossein Jadvar, Dr. Darlene Metter, Dr. Robert Schleipman (chair), Mr.
Michael Sheetz, and Ms. Megan Shober. Mr. Gary Bloom will serve as a non-voting subcommittee consultant.
03/30/2020 Accepted Open*
09/14/2020 4
The ACMUI endorsed the Patient Intervention subcommittee report, as presented, and the recommendations provided therein.
03/30/2020 Accepted Open Spring 2021 STATUS 1
2020 ACMUI RECOMMENDATIONS AND ACTION ITEMS 5
The ACMUI endorsed the Bylaws Subcommittee report, as presented, and the recommendations provided therein.
03/30/2020 Accepted Open*
09/14/2020 6
Dr. Metter formed a subcommittee to review the abnormal occurrence criteria, with the following in mind: (1) define patient harm in AO; (2) reassess current AO criteria; (3) define goals of AO criteria and reporting; and (4) are current AO criteria sufficient in regards to public health? Subcommittee membership includes: Mr. Gary Bloom, Dr. Ronald Ennis, Dr.
Hossein Jadvar, Mr. Zoubir Ouhib, Mr. Michael Sheetz, and Ms. Megan Shober. NRC staff resource: Dr. Katie Tapp.
(subcommittee on hold until further notice from staff) 03/30/2020 Accepted Open*
09/14/2020 7
The ACMUI endorsed the Interventional Radiologist Subcommitee report, as presented, and its recommendations provided therein.
03/30/2020 Accepted Open*
09/14/2020 8
The ACMUI tentatively scheduled its fall 2020meeting for September 21-22, 2020. The alternate date is September14-15, 2020.
03/30/2020 Accepted Open*
09/14/2020 9
The ACMUI endorsed the COVID-19 Subcommittee report, as presented, and its recommendations provided therein.
(4/30/20) 4/30/20 Accepted Open*
09/14/2020
- Action completed via the September 14, 2020 NRC Response Memorandum (ADAMS Accession No. ML20254A179) - pending formal closure by the ACMUI at the fall 2020 meeting.
2
OPEN FORUM NO HANDOUT
1 1
Medical Events Subcommittee Report Ronald D. Ennis, M.D.
Advisory Committee on the Medical Uses of Isotopes September 21, 2020
- Ronald D. Ennis, M.D. (Chair)
- Richard Green
- Darlene Metter, M.D.
- Michael OHara, Ph.D.
- Michael Sheetz
- Harvey Wolkov, M.D.
NRC Staff Resource: Donna-Beth Howe, Ph.D.
2 Subcommittee Members 1
2
2
- As begun in 2018, every two years the Medical Events Subcommittee will report on our review of events over the last 4 years 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 medical events (MEs).
- The Subcommittee reviewed the medical events for FYs 2016-2019.
3 Process Summary
- Two overarching themes remained
- 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
- One new issue identified
- Increase complexity of unsealed source administrations of newer agents may be leading to more equipment related MEs 4
3 4
3 35.200 Use of Unsealed Byproduct Material for Imaging and Localization 5
3/5 possibly preventable by time out Medical Events Summary 2016 2017 2018 2019 Total Cause Wrong drug 0
0 0
0 0
Wrong dosage 0
2 0
0 2
Wrong patient 0
1 0
0 1
Extravasation 0
1 0
0 1
Human error 0
0 0
1 (8 patients) 1 (8 patients)
Total 0
4 0
1 5
2016 2017 2018 2019 Total WD not done or incorrectly 1
2 1
2 6
Error in delivery
(# capsules) 1 1
0 1
3 Wrong dose 1
0 0
0 1
Equipment 0
0 1
4 5
Human Error 1
0 0
1 2
Wrong patient 1
1 0
1 3
Total 4
4 2
9 19 6
Time out could prevent 13/19 = 68%
Emerging increase in equipment issues 5/19 = 26% compared to 10% in last review 35.300 Use of Unsealed Byproduct Material, Written Directive Required Medical Events Summary 5
6
4 2016 2017 2018 2019 Total Applicator issue (e.g. movement during implant 1
0 0
0 1
Wrong site implanted (e.g. penile bulb) 1 1
1 1
4 Activity/prescription error (e.g. air kerma vs mCi, enter wrong activity in planning software) 0 1
0 1
2 Prostate Dose 18 5
11 3*
37 New device 0
0 1
0 1
Total 20 7
13 5
45 35.400 Manual Brachytherapy Medical Events Summary
- Still using dose-based criteria 2016 2017 2018 2019 Total Total MEs 20 7
13 5
45 Time out may have prevented ME 0
1 0
1 2
Lack of experience may have played a role 1
1 1
1 4
8 35.400 Manual Brachytherapy Medical Events Summary 7
8
5
- Many MEs in this category are no longer categorized as MEs due to change from dose to activity-based definition, although even in 2019, this definition continued to be used for some MEs.
- Lack of experience possibly plays a role in the true MEs of this type, but hard to assess to what degree in each case.
- In approximately 13% (down from 25% in last review) of cases, a time-out or enhanced retraining prior to performance of an uncommon procedure might have prevented the ME.
9 35.400 Manual Brachytherapy 2016 2017 2018 2019 Total Cause Wrong position 1
2 3
4 10 Wrong reference length 0
2 1
4 7
Wrong plan 1
0 2
0 3
Wrong dose/source strength 0
0 1
0 1
Machine malfunction 3
2 3
1 9
Software failure 0
2 (9 pts) 0 1
3 Total 5
8 (14 pts) 10 10 33 10 35.600 Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic unit Medical Events Summary 9
10
6 2016 2017 2018 2019 Location Breast 0
0 1
0 Gynecological 2
7 (14 pts) 7 8
Skin 1
0 1
0 Bronchus 0
0 0
0 Prostate 2
0 0
0 Brain 0
1 1
2 Total 5
8 (14 pts) 10 10 11 GYN tumors were most common site of ME.
35.600 Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic unit Medical Events Summary MEs that may have been prevented by timeout (wrong plans or dose)
- 2016 1/5 events
- 2017 0/8 events
- 2018 3/10 events
- 2019 3/10 events Total: 7/33 (21.2%) compared to 16% on last review 12 35.600 Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic unit 11 12
7 MEs caused by infrequent user This is difficult to determine based on information in NMED. If assumption is made about wrong position as surrogate for infrequent user.
- 2016 1/5 events
- 2017 2/8 events
- 2018 1/10 events
- 2019 1/10 events Total: 5/33 (15.2%) compared to 32% on last review 13 35.600 Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic unit 2016 2017 2018 2019 Total Medical Events 1
0 1
0 Cause:
Delayed seed removal (patient intervention) 1 1
Lost seed 0
Wrong implant site 0
35.1000 Radioactive Seed Localization Medical Events Summary 14 13 14
8 35.1000 Intravenous Cardiac Brachytherapy Medical Events Summary 2016 2017 2018 2019 Total Did not follow proper procedure 0
0 0
1 1
Tortuous vessel anatomy 0
0 1
1*
2 Catheter issue 0
0 1
0 1
Total 0
0 2
1 4
15
- AU felt this is patient intervention No time out issues Difficult to assess the unfamiliarity issue, but possibly played a role in some 2016 2017 2018 2019 Total Medical Events 3
0 1
0 Cause:
0 0
0 0
Back-up battery power source failure 0
0 1
0 Patient setup error 2
0 0
0 Patient movement 1
0 0
2 Wrong site (treatment plan) 0 0
0 0
35.1000 Gamma Knife Perfexion' and Icon' Medical Events Summary 16 15 16
9 2016 2017 2018 2019 Total Total Medical Events 13 15 14 15 57 Cause:
> 20% residual activity remaining in delivery device 9
7 11 9
36 Delivery device setup error 1
2 2
1 6
Wrong dose (treatment plan calculation error) 1 4
0 1
6 Wrong site (catheter placement error) 2 2
0 0
4 Wrong dose vial selected 1
4 5
35.1000 Y-90 Theraspheres Medical Events Summary 17 2016 2017 2018 2019 Total Total Medical Events 13 8
7 11 39 Cause:
> 20% residual activity remaining in delivery device not due to stasis 9
7 2
8 26 Wrong dose (treatment plan calculation error) 2 0
2 0
4 Wrong site (catheter placement error) 2 1
2 2
7 Wrong site (WD error) 0 0
1 1
2 35.1000 Y-90 SirSpheres Medical Events Summary 17 18
10 Overview Y-90 Microsphere MEs FY2014 - 2017 N=91 62, 65%
10%
12%
6%7%
Cause
> 20% residual not due to stasis Wrong dose (treatment plan error)
Wrong site (catheter placement error)
Device setup error Wrong dose vial/WD error FY2016 - 2019 N=96
- Review mechanics of Y-90 microsphere delivery device and setup procedures
- Confirm all data and calculations in treatment plan
- Perform Time Out to assure all elements of treatment are in accordance with Written Directive Actions to Prevent 35.1000 Y-90 Microsphere Medical Events 19 20
11 RSL Perfexion/Icon Y-90 Microspheres 2016 0/1 2/3 3/26 2017 0
0 3/23 2018 0/1 0/1 4/21 2019 0
0/2 7/26 Total 0/2 2/6 (33%)
17/96 (18%)
35.1000 Medical Events That May Have Been Prevented by Time Out RSL Perfexion/Icon Y-90 Microspheres 2016 0/1 2/3 1/26 2017 0
0 2/23 2018 0/1 0/1 2/21 2019 0
0/2 1/26 Total 0/2 (0%)
2/6 (33%)
6/96 (6%)
35.1000 Medical Events That May Have Been Attributed to Lack of Experience or Infrequent User 21 22
12
- Identity of patient via two identifiers (e.g., name and DOB)
- Procedure to be performed
- Isotope
- Activity
- Dosage - second check of dosage calculation and that the WD and dosage to be delivered are identical 23 Possible Elements of a Time Out
- Others, as applicable
- units of activity (LDR prostate)
- anatomic location
- patient name on treatment plan
- treatment plan independent second check has been performed
- reference length (HDR)
- implant site location (RSL) 24 Possible Elements of a Time Out contd.
23 24
13
- The subcommittee recommended that the NRC staff issue an Information Notice alerting Authorized Users to the themes identified herein.
- IN-19-07, Methods to Prevent Medical Events, was published on August 26, 2019.
(ADAMS Accession No. ML19240A450) 25 Subcommittee Response to Findings
- 10 CFR - Title 10 of the Code of Federal Regulations
- AUs - authorized users
- FY - Fiscal Year
- gyn - gynecological
- HDR - high dose-rate
- LDR - low dose rate
- mCi - milliCurie
- ME - Medical Event
- RSL - radioactive seed localization
- Y yttrium-90 26 Acronyms 25 26
U.S. Nuclear Regulatory Commission Advisory Committee on the Medical Uses of Isotopes Subcommittee on Medical Events Draft Report Submitted On: August 11, 2020 Subcommittee Members: Mr. Richard Green, Dr. Ronald D. Ennis (Chair), M.D., Dr. Darlene F.
Metter, Mr. Michael Sheetz, and Dr. Harvey Wolkov NRC Staff Resource: Dr. Donna-Beth Howe Charge The specific charge of this subcommittee is to annually review the medical events (MEs) with an eye to advising the ACMUI and NRC about emerging trends needing regulatory attention.
=
Background===
At the Fall 2018 ACMUI meeting this subcommittee initiated a new approach to reporting on MEs such that every 2 years the subcommittee will review medical events (MEs) occurring in the previous 4 years with the goal of identifying common themes within each section of 10 CFR Part 35 and discuss possible ways to prevent these MEs. The report herein is the second such in-depth 4-year review of MEs.
Findings The Subcommittee on Medical Events reviewed the Medical Events from FY 2016-19. Events from each section were reviewed in detail by a subcommittee member with expertise in the area. In the subcommittees review two years ago, we noted that a significant proportion of MEs might be prevented by the universal implementation of a time out prior to the procedure/treatment. In addition, we noted that a considerable number of events seemed to occur in situations in which the authorized user and team were performing a procedure/treatment with which they do not have much recent experience.
In the current review, the subcommittee found that the number of MEs, the types and the proportion possibly preventable by a time out and the proportion related to lack of experience, were about the same.
One new emerging trend was noted. In the delivery of unsealed byproduct material for which a written directive is required (10 CFR 35.300), there was an increase in the number of MEs related to equipment (e.g., catheter) issues. This is thought to be attributable to the increasing use of agents with more complex delivery (e.g., Lu-177 dotatate). The subcommittee anticipates this
trend will continue and warrants close observation. However, no specific intervention by NRC staff is recommended at this time.
A new Y-90 microsphere delivery device has been introduced by Sirtex. We will be watching for trends in MEs related to this problematic area with the introduction of this new device.
Concluding Remarks The subcommittee looks forward to performing an in-depth trend analysis in 2022 and next year will perform a focused one-year review of FY2020.
The subcommittee welcomes any comments and/or suggestions.
Respectfully Submitted, The Medical Event Subcommittee Ronald Ennis, MD, Chair
1 NonMedicalByproductMaterial Events:FY18andFY19 MichaelSheetz AdvisoryCommitteeontheMedicalUsesofIsotopes September21,2020 1
NonMedicalEvents ReportedbyMedicalLicensees
- NMEDeventreportedbymedicallicensee
- Doesnotincludemedicaleventsunder 10CFR35.3045or35.3047
- Includeseventsreportedunder:
- 10CFR35.3067(leakingsource)
- 10CFR20.2201(lostorstolenmaterial)
- 10CFR30.50(contamination)
- 49CFR171.15(transportationincidents) 2 1
2
2 NonMedicalEventCategories IdentifiedinFY18andFY19 Category FY18 FY19 Lost,Abandoned,orStolenSources 9
18 LeakingSealedSource 9
4 TransportationofRadioactiveMaterial 5
3 RadiationOverexposure 5
3 RadioactiveContamination 3
3 EquipmentMalfunction 1
4 Total 32 35 3
TotalNMEDEvents(AllCategories)
FY18andFY19 67 805 NonMedicalEventsfromMedicalLicensees AllOtherEvents 4
3 4
3 Lost,Abandoned,orStolenSources FY18andFY19
- LostI125RSLseed-9
- LostRAMshipment-6
- MissingI125/Pd103brachyseeds-3
- TemporarylossandrecoveryofRAM-3
- Abandonedcalibrationsources-2
- LostCs137dosecalibratorsource-1
- PatientremovalofI125brachyseeds-1
- Ir192sourcedeliverytowronglocation-1
- IncompleteshipmentofLu177-1 5
LeakingSealedSource FY18andFY19
- Ir192HDRsource-4
- Cs137dosecalibratorvial-3
- I125RSLseed-2
- Co57dosecalibratorvial-1
- Sr90intravascularbrachytherapydevice-1
- Co57calibrationrod-1
- Ge68phantom-1 6
5 6
4 TransportationofRadioactiveMaterial FY18andFY19
- Contaminatedpackage-4
- Vehicleaccident-2
- Damagedpackage-1
- Highexposurerate-1 7
RadiationOverexposure FY18andFY19
- PETradiopharmaceuticalproduction-3
- (50mSvDDE,690mSvSDE,600mSvSDE)
- Nuclearmedicineprocedures-2
- (130mSvDDE,580mSvSDE)
- Cyclotronrepair-1
- (720mSvSDE)
- C11andF18animalresearch-1
- (130mSvDDE)
- InterventionalradiologyusingY90microspheres-1
- (530mSvSDE) 8 7
8
5 RadioactiveContamination FY18andFY19
- Contaminationofhospitalroomfrompatient receivingpreviousI131therapy-2
- ContaminationofveterinaryclinicfromI131 treatmentofcat-2
- Patientcontaminationfromadministrationof F18-1
- Contaminationofhotlabfollowingbreakageof Tc99mvial-1 9
EquipmentMalfunction FY18andFY19
- Sr90IVBdevicesourceretractionfailure-2
- DefectiveHDRtransferguidetube-1
- HDRdeviceprematureterminationof treatment-1
- Rb82generatorSr82/85breakthroughlimits exceeded-1 10 9
10
6 OtherEvents-LandfillAlarms
- Detectionofshortlivedmedicalisotopesinmunicipal waste
- Nostandardreportingrequirement
- Decliningnumberofevents
- Canresultinsignificantresponseeffort FY14 FY15 FY16 FY17 FY18 FY19 113 114 71 18 17 6
11 Conclusions
- RelativelysmallnumberofNonMedicalevents
- Typeofeventsoccurringhaveminimalhealthand safetyimpact
- Decliningnumberoflandfillalarmresponsesreduces burdenonbothregulatorsandlicensees 12 11 12
7 Acronyms
- C11-carbon11
- CFR-CodeofFederalRegulations
- Co57-cobalt57
- Cs137-cesium137
- DDE-DeepDoseEquivalent
- F18-flourine18
- FY-FiscalYear
- Ge68-germanium68
- HDR-highdoserate 13 Acronyms
- I125/I131-iodine125/131
- IR192-iridium192
- IR-InterventionalRadiology
- IVB-IntravascularBrachytherapy
- Lu177-lutetium177
- mSv-milliSievert
- NMED-NuclearMaterialEventsDatabase
- Pd103-palladium103
- PET-PositronEmissionTomography 14 13 14
8 Acronyms
- RAM-RadioactiveMaterial
- Rb82-rubidium82
- RSL-RadioactiveSeedLocalization
- SDE-ShallowDoseEquivalent
- Sr82/85/90- strontium82/85/90
- Tc99m-technetium99metastable
- Y90- yittruim90 15 15
1 NewDrugDevelopmentand Labeling FrankLutterodt,M.S.,MSDRA DivisionofImagingandRadiationMedicine DivisionofRegulatoryOperationsSpecialty Medicine OfficeofRegulatoryOperations CenterforDrugEvaluationandResearch 2
Outline OverviewDrugDevelopmentProcess RegulatingtheUseofRadioactiveDrugsinBasic Research PreClinicalPhase ClinicalPhase NewDrugApplicationReviewandLabeling 1
2
2 3
Drug Development Process 4
RegulatingRadioactiveDrugsin BasicResearch RadioactiveDrugResearchCommittee(RDRC)
(21CFR361.1)
Forbasicscienceresearch Notforuseforimmediatetherapeutic, diagnosticorsimilarpurpose Nointenttodeterminesafetyoreffectiveness forclinicaluse https://www.fda.gov/drugs/scienceandresearchdrugs/radioactivedrug researchcommitteerdrcprogram 3
4
3 5
NewDrugDevelopmentProcess PreClinicalResearch Synthesisandpurification
- Targetaffinity
- Selectivityetc.
AnimalTesting
- PK
- Proofofconcept
- Toxicity
- Translationtohumans MeetingswithFDA https://www.fda.gov/media/109951/download 6
NewDrugDevelopmentProcess ClinicalPhase Phase1 Phase1approachesinvolveInvestigationalNewDrug Application(IND)andmayinvolve:
- 1. ExploratoryIND
- 2. TraditionalIND INDsaregovernedby21CFR312.21 INDsareusedtoestablishthesafetyor effectivenessofadrugtosupporttheapprovalofa newuse 5
6
4 7
NewDrugDevelopmentProcess ClinicalPhase Phase 1(ExploratoryIND)
AnexploratoryINDstudyisaclinicaltrialthat isconductedearlyinphase1, involvesverylimitedhumanexposure,and hasnotherapeuticordiagnosticintent.
Themainpurposeofthisapproachistofindpromisingdrug candidatestoenablethesponsortoproceedefficientlywiththe mostpromisingdrug.
https://www.fda.gov/media/72325/download 8
NewDrugDevelopmentProcess ClinicalPhase Phase 1(TraditionalIND)
TraditionalPhase1trialsusuallyinvolvehealthy volunteerstodeterminethedrugsmostfrequentand seriousadverseevents,andoften,howthedrugis metabolizedandexcretedbythebody Involveasmallnumberofparticipants,generallyinthe rangeof20to80subjects https://clinicaltrials.gov/ct2/aboutstudies/glossary 21CFR312.21https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.21 7
8
5 9
NewDrugDevelopmentProcess ClinicalPhase Phase 2 Phase2clinicaltrialgathersmoreinformation aboutadrugssafetyandeffectivenessinthe condition/diseasebeingstudied Largergroupofsubjects/participantsareenrolled Subjects/participantsreceivingthedrugmaybe comparedwithothersreceivingplacebo Safetyandshorttermadversereactionscontinue tobeevaluated 10 NewDrugDevelopmentProcess ClinicalPhase Phase 3 DuringPhase3,moreinformationisgathered aboutadrug'ssafetyandeffectivenessbystudying differentpopulationsanddifferentdosagesandby usingthedrugincombinationwithotherdrugs Studiestypicallyinvolvemoreparticipantsand efficacyendpointsareassessed Ifsafetyandefficacyareadequatelyconfirmed, clinicaltestingmayendatthisstepandaNewDrug Application(NDA)maybesubmitted 9
10
6 11 NDAReview Preclinicaldata(Pharmacology/Toxicology, ChemistryManufacturingandControls),and datafromtheclinicaltrialsarereviewedto assistFDAinmakingabenefit/riskassessment Afavorablebenefit/riskassessmentculminates inthereviewandapprovalofthedruglabeling 12 NewDrugLabelandLabeling Label Anydisplayofwritten, printed,orgraphicmatter ontheimmediatecontainer ofanyarticle,oranysuch matteraffixedtoany consumercommodityor affixedtoorappearingupon apackagecontainingany consumercommodity 21CFR1.3(b)/FD&CActsection201(k)
Labeling Alllabels,aswellasother written,printed,orgraphic matteraccompanyingthe product.
21CFR1.3(a)/FD&CActsection201(m) 11 12
7 13 Labeling CartonandContainerLabels PrescribingInformation(PI)PackageInsert PatientLabeling PatientInstructionsforUse,PatientInformation, MedicationGuide OperatorGuide(UserManual) 14 PrescribingInformation PhysicianLabelingRule(PLR)Formatwasimplementedin 2006 ContentsofthePrescribingInformation(PI)
Highlights TableofContents FullPrescribingInformation(FPI)
PregnancyandLactationLabelingRule(PLLR) 21CFR201.56and201.57 PhysiciansLabelingRuleRequirementsforPrescribingInformation http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/LawsActsandRules/ucm084159.htm 13 14
8 15 PLLR
- Labelformatchangetoreflectanintegrated assessmentofknownrisksrelevantto pregnancy,lactation,andinfertilitybasedon availableinformation/data DraftGuidanceforIndustry:Pregnancy,Lactation,andReproductivePotential:Labeling forHumanPrescriptionDrugandBiologicalProducts ContentandFormat http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidan ces/ucm425398.pdf PregnancyandLactationLabelingFinalRule http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeli ng/ucm093307.htm 16 GeneralTableofContentsinFPI BOXED WARNING 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 6 ADVERSE REACTIONS 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use 8.5 Geriatric Use 9 DRUG ABUSE AND DEPENDENCE 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 13.2 Animal Toxicology and/or Pharmacology 14 CLINICAL STUDIES 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION 15 16
9 17 PostMarketActivity Supplementalapplications INDs DrugAdvertising ManufacturerInspections ActiveSurveillance SafetyReports 18 ExamplesofRadiologicalDrugs RegulatedatCDER PositronEmissionTomographyGenerators Scintigraphic Agents MagneticResonanceImagingMedia UltrasoundContrastMedia IonicIodinatedContrastMedia NonIonicIodinatedContrastMedia NoniodinatedContrastMedia 17 18
10 19 Conclusion The discovery and development of new drugs can be long and complicated From conception to the marketing of a drug, FDA encourages sponsors/applicants to meet early in development Radiopharmaceutical and PET drugs are regulated by both NDA and labeling regulations (21 CFR 314, 21 CFR 201.56 and 201.57) 19 20
11 21 BackupSlides 22 NewDrugDevelopmentProcessLinks
- https://www.fda.gov/patients/learnabout druganddeviceapprovals/drugdevelopment process 21 22
12 23 LabelingforRadiopharmaceuticals andPETProducts ImaginginstructionsareplacedintheDosageandAdministrationsections IMAGINGINSTRUCTIONS ImageAcquisitionGuidelines TimingandDuration Location(head,body)
PatientInstructions(voiding)
DeviceParameters(e.g.2Dor3DPET,softwarereconstruction)
ImageDisplay Orientation ColoringDisplay ImageInterpretation Positivevs.Negative 23
1 DOSIMETRY METHODOLOGY UPDATE FOR REGULATORY GUIDE 8.39, PHASE 2 SEPTEMBER 21, 2020 OVERVIEW Phase 2 revisions to Regulatory Guide (RG) 8.39 are intended to update the dosimetry methodology Proposed direction will provide a versatile, realistically-conservative threshold for dosimetry The ease of basic thresholds and, if necessary, the ability to create patient-specific thresholds Thresholds are based on maximum bystander equivalent dose of 5 mSv and 1 mSv Breastfeeding infants are protected to the same level and the method is simplified Emerging technologies are easily supported with the new methodology RCD RADIATION PROTECTION ASSOCIATES 2
1 2
2 BASIC THRESHOLD PHILOSOPHY RCD RADIATION PROTECTION ASSOCIATES 3
Instruction Threshold Release Threshold No Regulatory Action ALARA Instructions 1 mSv to Bystander Dose to Bystander No Release Release Authorized Hold Patient 5 mSv to Bystander 10 CFR 35.75: release is authorized if bystander TEDE < 5 mSv written instructions required if bystander TEDE > 1 mSv Is A0 < 5 mSv basic threshold?
Start NO RELEASE Calculate patient hold time Provide patient instructions Is A0 < 1 mSv basic threshold?
Is A0 > 1 mSv infant threshold?
Is the patient breastfeeding?
Determine interruption time YES NO Calculate 1 mSv patient specific threshold Is A0 < 1 mSv patient specific threshold?
Is A0 < 5 mSv patient specific threshold?
YES YES YES NO Determine FO, FG, and FB Calculate 5 mSv patient specific threshold NO NO Preserve record if required YES YES Provide patient instructions NO NO Is breastfeeding interruption warranted?
NO YES RCD RADIATION PROTECTION ASSOCIATES 4
3 4
3 THE DOSE-RATE CONSTANT RCD RADIATION PROTECTION ASSOCIATES 5
Patient-Specific Activity Threshold Breastfeeding Activity Threshold Basic Measurement Threshold Basic Activity Threshold Breastfeeding Interruption Time Examples Dose-Rate Constant THE CURRENT METHOD (SIMPLISTIC AND CONSERVATIVE WITH ONLY MINOR PATIENT-SPECIFIC INPUTS)
RCD RADIATION PROTECTION ASSOCIATES 6
The estimated external time-integrated effective dose equivalent is:
1.44 k conversion constant exposure rate constant A0 administered activity Tr radiological half-life E occupancy factor r point/point distance In RG 8.39 Rev 0, gamma exposure constants come from several different sources without a consistent method of calculation. Additionally, point geometry is mandated, occupancy is overly simplistic, and pharmacokinetics can be applied if biological studies are available (but theres quite a bit of question here).
5 6
4 STANDARDIZED DOSE-RATE CONSTANT, pr The purpose of standardizing the gamma constant is:
to provide a consistent method of calculation, specifically for patient release;
to develop a tissue dose constant (point kernel) as opposed to an exposure constant;
to use the ICRP 107 nuclear decay database with an energy threshold of 10 keV;
to include primary photons, as well as bremsstrahlung from conversion & Auger electrons and beta emission;
to surround the source in a 2 cm tissue sphere (attenuation/buildup); and
to encapsulate implants in 50 m of titanium.
RCD RADIATION PROTECTION ASSOCIATES 7
COMPARISON OF DOSE-RATE CONSTANTS RCD RADIATION PROTECTION ASSOCIATES 8
Nuclide
Rev 0 pr (ICRP 107)
Smith &
Stabin 2012 Peplow 2020 67Ga 0.0203 0.0234 0.0217 0.0225 90Y 0.000798 0.000000362 99mTc 0.0204 0.0196 0.0215 0.0184 111In 0.0867 0.0736 0.0934 0.0615 123I 0.0435 0.0394 0.0481 0.0285 125I 0.0383 0.0301 0.0473 0.0125 131I 0.0594 0.0582 0.0594 0.0548 177Lu 0.00548 0.00489 0.00518 192Ir*
0.124a 0.122b 0.124c 0.117c all values in units of [mSv m2 GBq-1 h-1]
- Encapsulation: a200 m steel; b50 m titanium; cnone 7
8
5 THE BASIC ACTIVITY & MEASUREMENT THRESHOLDS RCD RADIATION PROTECTION ASSOCIATES 9
Patient-Specific Activity Threshold Breastfeeding Activity Threshold Basic Measurement Threshold Basic Activity Threshold Breastfeeding Interruption Time Examples Dose-Rate Constant CALCULATION OF THE BASIC ACTIVITY THRESHOLD, Q0
- 1.44
- integrated dose limitation r distance between patient and bystander pr dose-rate constant point kernel Tr physical radiological half-life Therefore, the basic activity threshold for release at 1 meter (point-to-point) for 99mTc is:
5 5
- 1 0.0196
- 1.44
- 6.02 29 RCD RADIATION PROTECTION ASSOCIATES 10 15.8 9
10
6 CALCULATION OF THE BASIC MEASUREMENT THRESHOLD, M0
Q0 basic activity threshold pr dose-rate constant point kernel r distance from source to instrumentation Therefore, the basic measurement threshold for release at 1 meter (point-to-point) for 99mTc is:
5 29
- 0.0196 1
0.58
RCD RADIATION PROTECTION ASSOCIATES 11 RCD RADIATION PROTECTION ASSOCIATES 12 Assume a given radionuclide has the basic instruction and release thresholds as shown and suppose 1 GBq of that nuclide has been administered. The activity is less than the basic thresholds for release and for instruction.
1GBq
Activity Threshold for Instruction Activity Threshold for Release No Regulatory Action ALARA Instructions 1 mSv to Bystander Dose to Bystander No Release Release Authorized Hold Patient 5 mSv to Bystander 1.5GBq 7.5GBq (1)
(5) 11 12
7 RCD RADIATION PROTECTION ASSOCIATES 13 Now suppose 10 GBq of that same nuclide has been administered to a different patient. This time the administered activity exceeds the basic threshold for instruction and for release.
10GBq
Activity Threshold for Instruction Activity Threshold for Release No Regulatory Action ALARA Instructions 1 mSv to Bystander Dose to Bystander No Release Release Authorized Hold Patient 5 mSv to Bystander 1.5GBq 7.5GBq (1)
(5)
THE PATIENT-SPECIFIC ACTIVITY THRESHOLD PATIENT-SPECIFIC MODIFYING FACTORS APPLIED TO THE BASIC THRESHOLD RCD RADIATION PROTECTION ASSOCIATES 14 Patient-Specific Activity Threshold Breastfeeding Activity Threshold Basic Measurement Threshold Basic Activity Threshold Breastfeeding Interruption Time Examples Dose-Rate Constant 13 14
8 Is A0 < 5 mSv basic threshold?
Start NO RELEASE Calculate patient hold time Provide patient instructions Is A0 < 1 mSv basic threshold?
Is A0 > 1 mSv infant threshold?
Is the patient breastfeeding?
Determine interruption time YES NO Calculate 1 mSv patient specific threshold Is A0 < 1 mSv patient specific threshold?
Is A0 < 5 mSv patient specific threshold?
YES YES YES NO Determine FO, FG, and FB Calculate 5 mSv patient specific threshold NO NO Preserve record if required YES YES Provide patient instructions NO NO Is breastfeeding interruption warranted?
NO YES RCD RADIATION PROTECTION ASSOCIATES 15 THE PATIENT-SPECIFIC ACTIVITY THRESHOLD, QM
Q0 basic activity threshold FO occupancy factor FG geometry factor FB biokinetic factor To provide realism, the licensee justifies that the patient-specific occupancy factor is 0.80, the geometry factor is 0.94, and the biokinetic factor is 0.84. Therefore, with a basic release threshold of 7.5 GBq, the patient-specific threshold for release, QM(5), is:
5 7.5 0.80
- 0.94
- 0.84 12 RCD RADIATION PROTECTION ASSOCIATES 16 15 16
9 RCD RADIATION PROTECTION ASSOCIATES 17 Using the patient-specific thresholds, and still considering the 10 GBq administered activity, the patient can be released with instruction.
10GBq
Activity Threshold for Instruction Activity Threshold for Release No Regulatory Action ALARA Instructions 1 mSv to Bystander Dose to Bystander No Release Release Authorized Hold Patient 5 mSv to Bystander 2.4GBq 12GBq (1)
(5)
THE OCCUPANCY FACTOR, FO Sample questions Do you have children?
Yes No Are you breastfeeding?
Yes No Youll return home using which form of transportation?
Plane Bus Train Subway Private Will family members travel with you?
Yes No How many others live in your home?
4 3
2 1
0 Do you normally sleep with someone in the same bed?
Yes No What is the total time (hours) of your return trip?
>10 8
6 4
<2 Will your return trip require a hotel stay?
Yes No RCD RADIATION PROTECTION ASSOCIATES 18 The licensee draws from a comprehensive patient survey to determine occupancy factor, FO.
17 18
10 DEVELOPMENT OF THE OCCUPANCY FACTOR Radiopharmaceutical Total Dose is Divided into Thirds 5 days 13 days The patient survey indicates that two individuals are candidates for the maximum bystander:
(1) the patients driver (8-hour trip)
(2) the patients co-worker (half-time; starting day 10)
RCD RADIATION PROTECTION ASSOCIATES 19 Driver Coworker
5 days 13days
x
x
=0.02 8
20
x x
+
x1 x
=0.05 RCD RADIATION PROTECTION ASSOCIATES 20 19 20
11 Familymembers Cohabitants Roommates Cotravelers Caregivers Coworkers
Fractionof timeinthe vicinityof patient
Xdays Y days
RCD RADIATION PROTECTION ASSOCIATES 21 RCD RADIATION PROTECTION ASSOCIATES 22 The geometry factor accounts for more realistic (less conservative) photon flux originating in the patient and impacting the bystander.
The assumption of a point source with a point receptor is no longer required.
FG is a function of both source/receptor geometry and distance between the two.
THE GEOMETRY FACTOR, FG
21 22
12 THE BIOKINETIC FACTOR, FB
A unitless surrogate for the residence time of a radionuclide in the body
Retention functions are specific to the chemical form of an administered agent and, therefore, FB is different for each pharmaceutical (and likely, each person)
We define FB as the ratio of integrated activity considering effective loss to that considering only radiological loss:
RCD RADIATION PROTECTION ASSOCIATES 23
CALCULATION OF THE BIOKINETIC FACTOR
Single-exponential retention function:
RCD RADIATION PROTECTION ASSOCIATES 24
Double-exponential retention function:
23 24
13 COMPARISON OF FB USING DIFFERENT MODELS demonstrating the variability in FB for Na131I retention.
[h]
- E1
- E2 f1 Te1 [h]
f2 Te2 [h]
FB 1.0 100 0.52 0.20 7.68 0.80 125 0.53 0.20 7.68 0.80 106 0.45 0.165 6.73 0.835 191 0.84 1
0.25 0.75 0.20 7.68 0.80 125 0.40 8
0.75 0.25 0.20 7.68 0.80 125 0.15 0.95 7.68 0.05 175 0.084 1
0.25 0.75 0.95 7.68 0.05 175 0.063 8
0.75 0.25 0.95 7.68 0.05 175 0.037 RCD RADIATION PROTECTION ASSOCIATES 25 Hyperthyroidism Thyroid cancer Single exponential THE BREASTFEEDING ACTIVITY THRESHOLD RCD RADIATION PROTECTION ASSOCIATES 26 Patient-Specific Activity Threshold Breastfeeding Activity Threshold Basic Measurement Threshold Basic Activity Threshold Breastfeeding Interruption Time Examples Dose-Rate Constant 25 26
14 Is A0 < 5 mSv basic threshold?
Start NO RELEASE Calculate patient hold time Provide patient instructions Is A0 < 1 mSv basic threshold?
Is A0 > 1 mSv infant threshold?
Is the patient breastfeeding?
Determine interruption time YES NO Calculate 1 mSv patient specific threshold Is A0 < 1 mSv patient specific threshold?
Is A0 < 5 mSv patient specific threshold?
YES YES YES NO Determine FO, FG, and FB Calculate 5 mSv patient specific threshold NO NO Preserve record if required YES YES Provide patient instructions NO NO Is breastfeeding interruption warranted?
NO YES RCD RADIATION PROTECTION ASSOCIATES 27 PROPOSED METHOD AND ASSUMPTIONS
Infant dose from external exposure (to body and to breast) and internal exposure from breastmilk consumption
two geometry factors (FG) with associated distance (r) for the external exposures
Pharmaceutical retention, R(t), describes activity over time in the mothers body and the derived concentration in breastmilk
Biokinetic factor:
Occupancy factor for breastfeeding: FO = 0.17
e.g., 30-minute duration every 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br />
Maximum breastmilk concentration assumed at tmax hours after administration
unless there is interruption, the time of first feeding is assumed at tmax (currently 3 hours3.472222e-5 days <br />8.333333e-4 hours <br />4.960317e-6 weeks <br />1.1415e-6 months <br />)
Breastmilk consumption rate: 40 mL/hr
Infant absorption fraction: f1 = 1
Infant dose coefficients taken from ICRP 128, RADAR, literature, etc.
RCD RADIATION PROTECTION ASSOCIATES 28 27 28
15 COMPARISON OF BREASTFEEDING INTERRUPTION TIMES RCD RADIATION PROTECTION ASSOCIATES 29 Radiopharmaceutical RG 8.39 Rev 0 ACMUI 2019 NUREG 1556 Rev 3 ICRP 106 2007 ICRP 128 2015 Stabin &
Breitz 2000 Sloan Kettering 2017 67Ga citrate 28 d 31 d 1 mo
> 3 wk
> 3 wk cessation 21 d 99mTc DTPA aerosol none 24 h none none none 24 h 99mTc RBC in vivo 24 h 24 h 6 h 12 h 12 h 12 h 24 h 111In WBC 6 d 5.7 d 7 d none none none 7 d 123I NaI 3 d 2.7 d none
> 3 wk
> 3 wk cessation 7 d 123I MIBG 24 h none 24 h
> 3 wk
> 3 wk 48 h 7 d 131I NaI cessation 32 d cessation
> 3 wk
> 3 wk cessation cessation EXAMPLES DEMONSTRATING THE METHODOLOGY RCD RADIATION PROTECTION ASSOCIATES 30 Patient-Specific Activity Threshold Breastfeeding Activity Threshold Basic Measurement Threshold Basic Activity Threshold Breastfeeding Interruption Time Examples Dose-Rate Constant 29 30
16 Y-90 MICROSPHERES
56 yo female administered 1.3 GBq 90Y resin microspheres
For the treatment of hepatocellular carcinoma RCD RADIATION PROTECTION ASSOCIATES 31 14GBq 68GBq 1.3GBq Basic Threshold for Instruction Basic Threshold for Release No Regulatory Action ALARA Instructions 1 mSv to Bystander Dose to Bystander No Release Release Authorized Hold Patient 5 mSv to Bystander I-131 FOR THYROID CANCER
40 yo male administered 7.4 GBq 131I as NaI
For the treatment of thyroid remnants and metastases RCD RADIATION PROTECTION ASSOCIATES 32 0.062GBq 0.31GBq 7.4GBq Basic Threshold for Instruction Basic Threshold for Release No Regulatory Action ALARA Instructions 1 mSv to Bystander Dose to Bystander No Release Release Authorized Hold Patient 5 mSv to Bystander 31 32
17 I-131 FOR THYROID CANCER
40 yo male administered 7.4 GBq 131I as NaI
For the treatment of thyroid remnants and metastases RCD RADIATION PROTECTION ASSOCIATES 33 2.6GBq 13GBq 7.4GBq 5
0.31 0.40 0.72 0.084 13 1
0.062 0.40 0.72 0.084 2.6 Patient Threshold for Instruction Patient Threshold for Release No Regulatory Action ALARA Instructions 1 mSv to Bystander Dose to Bystander No Release Release Authorized Hold Patient 5 mSv to Bystander RCD RADIATION PROTECTION ASSOCIATES 34 QUESTIONS?
33 34
ACMUI Training September 22, 2020
[CLOSED MEETING PORTION]
NO HANDOUT
1 Updatesfromthe MedicalRadiationSafetyTeam September22,2020 LisaDimmick,TeamLeader,MedicalRadiationSafety MedicalSafetyandEventsAssessmentBranch DivisionofMaterialsSafety,Security, State,andTribalPrograms OfficeofNuclearMaterialSafetyandSafeguards COVID19
- NRCPreparationforTemporaryRegulatoryReliefRequests
- Developedguideandatemplatetoquicklyprocess anticipatedexemptionrequests.
- Publicmeetings
- April22,2020meetingtogatherstakeholderinput (meetingsummaryavailableatML20122A253)
- April30,2020ACMUICOVID19Subcommitteemeeting (subcommitteereportavailableatML20125A148)
- May13,2020SNMMITownHall
- May5,2020LettertoNRCMedicalLicensees
- Enclosurecontainsatableof10CFRParts19,20,30,and35 requirementsforwhichtheNRCmayconsiderexpedited requestsfortemporaryexemption.
- ML20126G385and https://www.nrc.gov/materials/miau/medusetoolkit.html 2
1 2
2 COVID19
- Updatedthetableforexpeditedexemptionsduring COVID19,August2020(ML20233B145)
- Continuallyreviewinginformationreceivedfrom medicalprofessionalsocietiesandmedicallicensees regardingtheimpactoftheCOVID19emergency.
- Virtualtraining/trainingmodificationrequests
- CBNC
- ASNC,SNMMI,ACR,ASTRO
- Elekta
- NorthStar 3
AuthorizedUser TrainingandExperience
- SECY200005,RulemakingPlanforTrainingand ExperienceRequirementsforUnsealedByproduct Material,January13,2020(ML19217A318)
- Recommendedrulemaking:(1)removeprescriptive trainingandexperience(T&E)requirements,(2)NRCand AgreementStatesnolongerreviewandapproveT&E, (3) authorizedusersmustbecredentialedbyarecognized medicalspecialtyboard,and(4)maintainhighlevelboard recognitioncriteria.
- RecentletterstotheCommissionfromurologists supportingtherecommendedrulemaking.
- SECY200005isstillbeingreviewedbytheCommission.
4 3
4
3 PatientRelease
- SECY180015,StaffEvaluationoftheU.S.Nuclear RegulatoryCommission'sProgramRegulatingPatient ReleaseAfterRadioisotopeTherapy,January29,2018 (ML17279B139)
- Brochure-WhatYouShouldKnowAboutTreatments WithRadioactiveDrugs,May2019(ML19121A242)
- Phase1updateofRegulatoryGuide8.39Rev1,Release ofPatientsAdministeredRadioactiveMaterial,April 2020(ML19232A081) 5 PatientRelease
- NoticeofDocketingforthePeterCranepetitionwas publishedintheFederalRegister onApril13,2020and subsequentlywithdrawnbythepetitioneronJuly10, 2020
- Whatsnext?
- PatientReleasevideotargetrelease:November2020
- Phase2updateRegulatoryGuide8.39targetrelease:
spring2022 6
5 6
4 NewProcessforReviewingEmerging MedicalTechnologies
- TheMedicalTeamistransformingitsprocess for reviewingemergingmedicaltechnologies (EMTs). Thebenefitsofthisnewprocessarethatit:
- Streamlinesthereviewprocessandlicenseguidance development
- Providesacostsavingsinbothtimeandstaffresources;
- RemainsinclusiveofNRCregional,AgreementState,and ACMUIcontributiontolicenseguidancedevelopment;and
- Ensuresconsistencyandamoreuniformapproachto licenseguidancedevelopment.
7 NewProcessforReviewingEmerging MedicalTechnologies Medical Team individual with support develops licensing guidance Standing Committee,
- ACMUI, Agreement States, Regions review Resolve comments Concur and issue licensing guidance Total time 8 months (6 months savings) 8 7
8
5 RulemakingPlan:
EmergingMedicalTechnologies
- Rulemakingplanwillprovideoptionstocodifylicensing requirementsforEMTsandaddresscalibrationand dosemeasurementissuesfor Rb82generators.
- RulemakingoptionsrangefromonlyaddressingRb82 generators,codifyingrequirementsforonlycertain EMTs,orcodifyingmoreperformancebasedlicensing requirementsforEMTsacrossmostof10CFRPart35
- RulemakingplanwillgototheCommissioninDecember 2020.
- ACMUIwillreceiveacourtesycopyofthedraftrulemaking planinOctober2020.
9 Extravasation
- HouseandSenateFY20appropriationbillsrequireda reportonupdatestoinjectionqualitymonitoring, classification,andreportingrequirementsregarding extravasations.
- CongressionalreportsubmittedonMarch17,2020 (ML20050W302) 10 9
10
6 Extravasation
- PetitionforrulemakingPRM3522,Reporting NuclearMedicineInjectionExtravasationsasMedical Events,wassubmittedtotheNRConMay18,2020
- FindmoreinformationonthepetitionontheFederal rulemakingwebsite,https://www.regulations.gov,by searchingDocketIDNRC20200141
- Publiccommentperiodonthepetitionwillrunfrom SeptemberthroughNovember2020 11 Extravasation
- MedicalTeamstaffiscoordinatingtheirevaluationof whetherextravasationsshouldbereportedasmedical eventswiththepetitionreviewworkinggroup.
- MedicalTeamwillholdapublicmeetingformedical communityinputonextravasationsandmedicalevent reporting.(TentativelyscheduledforDecember8,2020)
- MedicalTeamwillseekACMUIreviewoftheir preliminaryrecommendationsinearlyMarch2021.
- Adecisiononwhethertoacceptthepetitionfor rulemakingwillbemadebyJune2021.
12 11 12
7 VeterinaryRelease
- MedicalTeamisevaluatingarequesttoreleasedogs followingtreatmentofosteoarthritisusingaSn117m colloid.
- Veterinaryreleaseissubjectto10CFRPart20limitsfor membersofthegeneralpublic,whichare:
- 100mremperyear
- 2mreminanyonehour
- Theproposedreleaseprocedurecontainsapre screeningquestionnairetodeterminetheneedto modifyorstopanytypicalinteractions (e.g.,co sleeping) foradurationoftimeafterrelease.
- Staffisstillreviewingthisrequest.
13 UpcomingMeetings FDANRCWorkshopEnhancingDevelopmentofEmerging Technologies:RadiopharmaceuticalsandRadiologicalDevices, October14,2020,8am5pm.https://www.fda.gov/drugs/news eventshumandrugs/fdanrcworkshopenhancingdevelopment emergingtechnologiesradiopharmaceuticalsandradiological AAHPandMedicalHealthPhysicsSectionSpecialSession TherapyPatientReleaseIssues,October15,2020,25pm.
InternationalConferenceonRadiationSafety:ImprovingRadiation ProtectioninPractice.IAEA,November920,2020.
https://www.iaea.org/newscenter/news/comingupfullyvirtual iaearadiationsafetyconference CommissionMeetingwiththeAdvisoryCommitteeontheMedical UsesofIsotopes(ACMUI),November18,2020,10am-12pm Extravasationpublicmeeting,December8,2020.Meetingdetails tobeprovidedatalaterdate.
14 13 14
8 Acronyms
- AAHPAmericanAcademyofHealthPhysics
- ACMUIAdvisoryCommitteeonMedicalUsesofIsotopes
- ACRAmericanCollegeofRadiology
- ASNCAmericanSocietyofNuclearCardiology
- ASTROAmericanSocietyforRadiationOncology
- CBNCCertificationBoardofNuclearCardiology
- EMTEmergingMedicalTechnology
- FDAU.S.FoodandDrugAdministration
- FYFiscalYear
- IAEAInternationalAtomicEnergyAgency 15 Acronyms
- Mrem millirem
- Rb82rubidium82
- Sn117mtin117m
- SNMMISocietyofNuclearMedicineandMolecularImaging
- T&E-trainingandexperience 16 15 16
OPEN FORUM NO HANDOUT
Sunday Monday Tuesday Wednesday Thursday Friday Saturday 28 1
2 3
4 5
6 7
8 9
10 11 12 13 NRC RIC NRC RIC NRC RIC APhA Annual Meeting APhA Annual Meeting 14 15 16 17 18 19 20 APhA Annual Meeting APhA Annual Meeting 21 22 23 24 25 26 27 28 29 30 31 1
2 3
PESASH PESACH 4
5 March 2021 Notes NRC's Regulatory Information Conference - March 9-11 American Pharmacists Association (APhA) Annual Mtg. - March 12-15 Passover (Pesach) begins March 28 - April 4 (work permitted March 30-April 2 with restrictions)
Sunday Monday Tuesday Wednesday Thursday Friday Saturday 28 29 30 31 1
2 3
PESACH 4
5 6
7 8
9 10 EASTER PESACH 11 12 13 14 15 16 17 AAPM Clinical 18 19 20 21 22 23 24 AAPM Clinical AAPM Clinical NCRP AAPM Clinical NCRP CIRMS CIRMS CIRMS 25 26 27 28 29 30 1
2 3
April 2021 Notes American Association of Physicists in Medicine (AAPM) Spring Clinical Meeting - April 17-20 National Council on Radiation Protection & Measurements (NCRP) Annual Meeting - April 19-20 Council on Ionizing Radiation Measurements & Standards (CIRMS) Annual Meeting - April 21-23