ML19308C187

Pre-Submittal Meeting with Exubrion Therapeutics, Meeting Handouts, November 6, 2019

ML19308C187
Person / Time
Issue date:	11/06/2019
From:	Office of Nuclear Material Safety and Safeguards
To:
Wu, Irene NMSS
References
Download: ML19308C187 (10)

Text

PreSubmittal Meeting with Exubrion Therapeutics November 6, 2019 Medical Radiation Safety Team Medical Safety and Events Assessment Branch Division of Materials Safety, Security, State, and Tribal Programs Office of Nuclear Material Safety and Safeguards Agenda

• Introductions and opening remarks

• NRC presentation

• Process

• Schedule

• Necessary content for application

• NRC and Exubrion discussion

• Public comments 1

Notice of Review Presubmittal Application Intent (NOI) and meeting submitted submitted resubmit No Acceptance Public meeting letter issued Accepted summary for issued review? Acceptance Yes Review Requests for RAI Review Additional responses and Information (RAIs) submitted resubmit Issued No RAI Draft Technical Final TE responses Evaluation (TE)

Yes issued acceptable? issued 3

Tentative Schedule Milestone Tentative Date for Completion Presubmittal meeting held November 6, 2019 Application received Late November 2019 Acceptance review completed MidDecember 2019 RAIs issued MidJanuary 2020 RAI responses received MidFebruary 2020 Draft TE issued MidApril 2020 Comments on Draft TE received Late April 2020 Final TE issued Summer 2020 4

2

Public Dose Requirements

• 20.1301 Dose limits for individual members of the public (paraphrased)

• (a) Each licensee shall conduct operations so that

• (1) The total effective dose equivalent to individual members of the public from the licensed operation does not exceed 0.1 rem (1 mSv) in a year, and

• (2) The dose in any unrestricted area from external sources does not exceed 0.002 rem (0.02 millisievert) in any one hour 5

Reporting Criteria

• 10 CFR 20.2203 Reports of exposures, radiation levels, and concentrations of radioactive material exceeding the constraints or limits.

• (a) Each licensee shall submit a written report within 30 days after learning of any of the following occurrences:

• (2) Doses in excess of any of the following:

• (iv) The limits for an individual member of the public in 10 CFR 20.1301; 6

3

Public Dose Considerations

• These public dose limits apply to every dog, not to the average

• Licensees are responsible to ensure these dose limits are met

• Strong screening criteria are necessary to ensure public dose limits are met for proposed dose rate at time of release

• Instructions should not be relied upon as the primary way to ensuring dose limits are met 7

Public Dose Considerations (cont.)

• 10 CFR 20.1301(a)(2) - dose limit of 0.002 rem (0.02 millisievert) in any one hour

• This dose limit is not an average but for any one hour

• Distances under a foot need to be considered.

• Screening criteria maybe necessary. Instructions can support screening criteria, but cannot be the primary method which the regulation is met.

8 4

Radiation Area

• 10 CFR 20.1003 Radiation area means an area, accessible to individuals, in which radiation levels could result in an individual receiving a dose equivalent in excess of 0.005 rem (0.05 mSv) in 1 hour1.157407e-5 days <br />2.777778e-4 hours <br />1.653439e-6 weeks <br />3.805e-7 months <br /> at 30 centimeters from the radiation source or from any surface that the radiation penetrates.

9 Current Issues

• Justification seems to focus on averages instead of individual dogs. Public dose limit is per dog.

• Current dose release proposal of 0.5 mR/hr at a 1 meter

• Significantly higher than recommended for Iodine131 in cats, which has a shorter half life

• Results in a radiation area. Proposed maximum dose rate at time of release cannot exceed this limit.

• Very unlikely 2 mrem in any one hour could be met following dog release

• Close contact would result in high doses very quickly, cannot be ignored 10 5

Current Issues (cont.)

• Attenuation

• Measurement data needed. Attenuation for different size dogs needs to be demonstrated.

• Geometry, distances, and dose rate should be included

• Close contact (i.e. messages, dog with legs over person, lifting the dog, etc.)

• Assumptions need to be conservative or licensee will need strong assurance assumptions are met for each animal

• Figures to show distances would be helpful

• What about dose to a child?

• Licensees procedure if a dog cannot be released immediately 11 Current Issues (cont.)

12 6

Example Assumption Needing more Justification

• Additionally, in most postures of lapsitting, the dogs body will serve as a shield for most of the human torso for radiation coming from the dogs legs or the dog would be in such a position that the average distance would be a foot or more, i.e.

stretched out perpendicular to the humans legs or with the dogs legs pointed towards the humans knees. Therefore, dose rates and occupancy factors at a distance of 3 inches are not discussed further.

13 Information Needed*

• Introduction

• Proposed Generic Procedures for Release

• Proposed Screening Criteria

• Proposed Generic Instructions

• Technical Basis Supporting Proposal

• Review will only consider information submitted as part of proposal.

14 7

Introduction

• Scope

• Identify information applicants will need to provide

• Administration Limitations, i.e.

• Maximum activity/isotope/form

• Location of treatment

• Minimum spacing between procedures

• Number of dogs treated per owner/home over what time period

• Training specific to Sn117m use 15 Proposed Generic Procedures for Release

• Assumptions and limitations

• Release dose rate or method to calculate dog specific release dose rates

• Screening criteria

• Instructions

• Survey, i.e.

• Location

• Survey meter

• Contamination

• Documentation

• Boarding Information 16 8

Proposed Screening Criteria

• Define licensees responsibility to ensure 10 CFR Part 20 is met for each individual dog within their unique circumstances.

• Describe the screening criteria you propose the licensees submit with the applications.

• Provide procedural steps on how licensees are given highconfidence that screening is sufficient to ensure public dose limits are met.

• If screening initially shows dogs behavior could result in public dose limit being exceeded, describe if and how licensees will allow owners to demonstrate dogs can meet modified behavior to allow them to be re screened.

17 Proposed Generic Instructions

• Distances

• Time lines

• What to do in the case of emergency or death

• Owner signature

• Describe dose if instructions are not followed 18 9

Technical Basis Demonstrating Compliance

• Defend assumptions

• Provide attenuation data

• Provide dose rate data for different size animals

• Figures demonstrating distances and geometry

• Justification for expected animal behavior

• Retention studies

• Total doses for:

• Maximum doses with instructions and screening compliance

• Maximum dose with poor instruction compliance

• Maximum likely dose with no instructions and screening criteria 19 10