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2019 BLIP/RRPL Isotope Program

Biennial Science and Technology

Review

Isotope Program Technical Progress

Cathy S. CutlerMIRP Director

Collider-Accelerator Department

Brookhaven National Laboratory

• First to use a high energy proton accelerator to produce isotopes (1972)

• BLIP utilizes the beam from the 200-MeV Linacthat injects the Booster, which leads to AGS and RHIC accelerators (nuclear physics)

• Excess Booster pulses (~90%) are diverted to BLIP. Energy is incrementally variable from 66-202 MeV

• The BLIP beam line is a synergistic operation with nuclear physics programs for more cost effective isotope production

• In 2016, implemented beam rastering and increasing linac current to increase isotope production capabilities

Brookhaven Linac Isotope Producer (BLIP)

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Target basket

Brookhaven Linac Isotope Producer (BLIP)

BLIP schematics

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BLIP target stack

0 20 40 60 80 100 120 140 160 180 200

Proton energy, MeV

232Th(p,2p6n)225Ac

68Zn(p,2p)67Cu

natRb(p,xn)82Sr82Sr - API for Bracco’s

Cardiogen-82® generator75As(p,4n)72Se

natGa(p,xn)68Ge

75As(p,4n)72Se

86Sr(p,n)86Y

206Re/209Re

45Sc(p,2n)44Ti

Opportunities for Isotope Productionand R&D at BLIP

BLIP beam raster system

• Reduction in localized target heating

• Enables increase in beam current from 100 µA to 165 µA (greater isotope yields)

• Greatly lowers possibility of target failures

Linac intensity upgrade• Phase 1 increased current to

165 µA

• Phase 2 Will increase current to 250 µA by increasing pulse length

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1

2

3

4

5

1 8 15 22 29 36 43 50 57 64 71 78

0

1

2

3

4

5

1 9 17 25 33 41 49 57 65 73 81

BLIP Beam Enhancements

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QA in FY2018

• All thirteen production batches met the specifications for Sr-82 API final

product.

• One customer complaint, dated March 6, 2018, on “vial not crimp-sealed”

resulted in five corrective actions, completed on April 17, 2018.

• DraxImage audit performed on Nov. 6-7, 2017, 1 major and 1 minor

observations, corrective actions were completed and closed in May 2018

• Major acceptance criteria not defined for the HPGE

• Bracco audit performed on Sept. 11-12, 2 major observations, corrective

actions to be completed by Feb. 2019.

• No policy for electronic signatures, Document review of reports and validations

• Submission of a response document to “List of Questions” relating to JBI

ASMF Assessment Report, completed in Oct. 2018

• Two stability Studies, completed in July and Oct. 2018

• Annual Particle Count Report, completed in Sept. 2018

• Implementation of procedures to fully comply with PET cGMP, completed in

Dec. 2018

• Annual Product Quality Review, completed in Dec. 2018

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QA in FY2019• No failures, no complaints, no recalls, no adverse events

or inconsistencies

• Procedures and Specifications for Th material and target

specifications, irradiation report

• Facilitating Tri-Lab Ac-225 DMF at ORNL

• Developed resource loaded schedule for BNL Ac-225

DMF

• IQ, OQ & PQ for the new HPGe detector, completed in

Jan. 2019

• Internal QA Audit, TBD (Q2/Q3)

• ICP-OES software upgrade compliance with cGMP Data

Integrity requirements, TBD (Q3/Q4)

• Stability Study, TBD (Q3/Q4)

• Annual Particle Count Report, TBD (Q3/Q4)

• Annual Product Quality Review, TBD (Q3/Q4)7

• 19 MeV, 250 μA

• Utilize for work force development

• Stony Brook and Hunter interested in developing training programs involving cyclotron

• Quality persons training

• Radioisotope production and separations

• Cross sections and targetry with nuclear data program

▪ One FTE to support these efforts will be required in the future.

▪ Engaging faculty from Stony Brook and Hunter College

▪Radiometal production

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TR19 Cyclotron

Ebco Technologies Inc.TR19 Cyclotron

The cyclotron was completely installed for the PET program

Refurbishment of Cyclotron

• Install new Chiller, re-establish power, hook-up to water heat exchanger, control systems, access control systems, refurbish Cryo compressor, cold heads, roughing vacuum, pumps and power supplies

• Replace steel shot and fix shielding holes

• Brought in an outside expert to provide guidance

• Company that built the cyclotron has been on site twice to aid in development of a punch list to prepare for the low energy beam test

• Under the supervision of the company’s expert we were able to turn on all the subsystems and established a new punch list to move forward

• Access controls is continuing work on the safety interlock system

• Refurbished vacuum and wiring on one of the target station

• Electrician are working on bringing power to the control room to LOTO critical devices: RF, inflector power supply and bias power supply

Refurbishment of Cyclotron

• Company brought in twice to develop punch list and test

subsystems.

• All individual subsystems tested, HV rack, RF rack and

vacuum.

• Work continues with access controls for the interlock

systems

• Low power beam test next after approval received from

BHSO

• Develop procedures, bring company back to train

operators on operations and maintenance

• Gain experience on low level runs

• Perform IRR and ARR

• Complete Ra Targetry

Low Energy Cyclotron

Targetry for Cross sections Determinations Using Tandem

Samples:

• 100 ul 0.05M Nitric

• 10ml IPA

• Experiment

• 300 V 20 mins

• Current: 30 mA

Estimated Date Authorization Step

9-2018 RSC Approval of Personnel Protection System (PPS) Design

12-2018 ACSI visit to begin rehabilitation of cyclotron,Safety Analysis and Controls Developed for Low Power Beam Test

1- 2019 Lab ESH Committee Recommends Approval of Accelerator Exemption for Low-Power Test-Beam and RF Testing

2-2019 Submit Exemption Request to BHSO

Submit SAD and ASE to Lab ESH CommitteeACSI returns to rehabilitate cyclotron; low-power testing performed

?-2019 Deployment and validation of PPS completeSubmit SAD and ASEs for TR19, APF, BLIP and TPL to BHSO

?-2019 Perform IRR and submit to BHSO

?-2019 Request BHSO authorization to commission TR19 with low-hazard

targets

?-2020 Perform IRRs and ARRs for TR19, APF, BLIP and TPL

Request BHSO authorization for routine operations of same

Current Schedule for Cyclotron

Commissioning

• Extra 1 in. lead shielding for hot cell

• In preparation for large-scale production

of Sr-82 and Ac-225

• To be installed piece-wise throughout

the FY2017 season

• New HPGe detector for daily water

sampling with electric cooling

• Releases handheld transspec for other

projects in TPL

• Installed FY2017

• Replaced aging fork-lift truck with

new one

Completed (or In Progress) BLIP Upgrades

Packaging Area

Sr-82 Processing

Sr-82 Dispensing

Acid Scrubber

Target Can Delivery from BLIP

FumeHood

Ro

ll-u

p d

oo

r

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RbCl Target Opening (FY2016)

Biodex Storage Area (FY2016)

TPL Upgrades Industrial and R&D Target Can Opening

Industrial and R&D Processing and Dispensing

Waste Storage

CCure access control areas(FY2016)

Change of Manipulator Grips to Pistol-Type (BLIP & TPL)

• Facility upgrades funds from FY15 ($217k) and

infrastructure funds ($40k):

• Covered pistol grip conversion for all installed

manipulators

• Better ergonomics - great feedback from operators

• FY2017: 6 conversions, purchase 1 Model 7

manipulator

• FY2018: 6 conversions

Old style grips

Pistol grips

Ac-225 target opener

▪ Based on LANL design

• Painted floor in TPL and scrubber room

• Improved waste removal process

• Improved acid scrubber trunks

• Sr-82 hot plate controller improvement

• 2-57A is an alpha lab

• Hand and foot monitor

• HpGe detectors

• Set up more alpha probes

Target Processing Lab Upgrades

• Refurbished HB2, 3, 4 and 5 for Sr-82, research, and industrial isotope

production

• Decontaminated, repainted & lined with plastic

• Installed all new new water line and valve, acid scrubber enclosure and trunk,

manipulator boots and jaws, laboratory parts

• Cu-67 to be processed in HB3 - currently a low natural Cu environment

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Hot Box Refurbishments

20Before After

PLC Hotplate

for Sr-82 Processing▪ Reduces risk to program

▪ Minimizes handling and spill potential

▪ PLC controlled temperature with

thermocouple feedback minimizes

potential for release to ventilation

system

▪ Grounded for electrical safety

▪ Cost effective

▪ Off-the-shelf ceramic hot plate

▪ Electronics are outside hot box to

prolong longevity

▪ Better ergonomics

▪ Reduces the need to change hot-

plates every 2 processes

Remaining TPL Upgrades

Spac

eItem

Cost

($)Risk Justification Year

Ops or

New $

56

Additional lab

space for Quality

control

300k Med

Need to add additional QC equipment for Ac-

225 and current lab is full and ventilation is

not adequate

2019 Ops

2-66

Clean, insulate

and repair AHU-1

ducting

300K MedIncrease air cleanliness in cGMP and

other work areas2019 Ops

TPL

Room 66

Ventilation Panel

Upgrade

200-

300KHigh

Improve air flow monitoring in the TPL

area2020 New

66

Split TPL hood

into 2: research

and production

side

400K Med

Reduce cross contamination; pharmacy hood

would provide better shielding for packaging

Biodex containers

2022 New

66C

New cask and/or

delivery system for

transfer casks

50K MedIncrease ease of use of 66C hot cells for

waste and target movement2022 New

New Transfer

Cask ? Med Single point failure 2020 New

Renovations of Lab 2-66C

• Renovation will allow for

production of radiochemical

grade isotopes at the Curie

level

• Work to include:

• Replace existing fume hood

with a smaller radiological

fume hood

• Install new hot cell

• Modify two existing hot cells to

include additional shielding

Preliminary cost estimate: $1.96M

Preliminary construction schedule: 2 months

• ICP-OES routine maintenance and software update for data integrity

• Loss of industrial knowledge in targetry• Revised procedure to include more rigor and specifications

• Requested more than one person be trained on targetry

• Implemented log book

• BNL Accelerator Review• Will be discussed further in EHSQ talk

Operational Improvements

• ICP-OES was a single point-failure for Sr-82 QC• Sr-82 specific activity is a requirement for COA

• Purchased new AA spectrometer • To measure cold Sr content in Sr-82 final product

• Relatively inexpensive at $25k compared to ~$200k for new ICP

• Installed in QC Lab

• Process of purchasing a second Perkin Elmer ICP-OES $80K

Mitigated Single Point Failure

MIRP Investigation Procedure

• 13.10.1, “Independent Assessment, Independent Verification and Nonconformance Reporting and Corrective/Preventive Action Tracking”

• 13.10.1.a, “Medical Isotope Research and Production (MIRP) Evaluation Form”

• Reason for evaluation: ☐ Customer-feedback

☐ Customer-complaint

☐ Customer-request

☐ Observation

☐ Deviation

☐ Out Of Specification (OOS)

MIRP Investigation Procedure (Cont’d)

• Description of Event/Issue

• Evaluation participants (i.e. QA, SME, Operator)

• Action initially taken, if any

• Fact finding

• Analysis – perform a thorough assessment of facts

• Evaluation Results including Root Cause

• Corrective/Preventive Action

• ATS tracking of corrective actions, independent verification and closeout

• A review of adequacy of corrective actions in yearly Product Quality Review.

Thick Target Failure Investigation• Reason for evaluation: ☒ Observation

• Description of Event/Issue: 2/8/19, BLIP Operator noticed elevated air emissions & sample radiation levels, indicating target failure.

• Evaluation participants: J. Eng (QA), J. Ziegler & H. Chelminski (BLIP Operators), D. Medvedev (MIRP Scientist) & C. Cullen (C-AD Engineer).

• Fact Finding and Analysis:• Failed thick target received charge of 2,854 µA-hrs for about 18 hrs with

average current of 161 µA.• Thick target failed when beam current reached the peak point at 158 µA,

corresponding to beginning of elevated air emissions.• Comparison with previous targets and irradiation conditions (highest current

we’ve ever run) indicate insufficient cooling. • Recent study shows that re-programming the raster improved heat distribution

resulting in lower max temperature on targets.

• Contributing Cause: Target Cooling is insufficient for this energy deposition profile.

• Root Cause: Not enough statistical data to identify.

• Corrective Action: Re-program the beam raster to improve heat distribution on the targets.

Thin Target Failure Investigation• Reason for evaluation: ☒ Observation

• Description of Event/Issue: 2/20/19, BLIP Operation noticed elevated air emissions, indicating target failure.

• Evaluation participants: J. Eng (QA), J. Ziegler & H. Chelminski (BLIP Operators), D. Medvedev (MIRP Scientist) & C. Cullen (C-AD Engineer).

• Fact Finding and Analysis:• Various beam stop materials attempted in the past not long-lasting. Recent attempt using

Cu in Inconel capsule showed similar results as previous attempts, indicating the design still not optimized.

• The targets had 142,775 µA-hrs for about 888 hrs with average current of 159 µA.

• BLIP emission plot shows that the beam stop failed at the highest beam current of 169 µA, indicating the target heat deposition/cooling process was marginal.

• When the beam stop failed, the separated window fell onto the thin target, restricting the target cooling water flow and causing the thin target to fail.

• Contributing Cause:• Actual performance of the beam stop was worse than predicted by theoretical analysis

• Inadequate cooling.

• Root cause of failed beam stop: Not enough statistical data to identify

• Root cause of failed thin target: The failed beam stop leaned onto the thin target restricting the cooling water flow.

• Corrective Action: Re-program the beam raster to improve heat distribution on the targets.

Low Sr-82 Yield Investigation

• Reason for evaluation: ☒ Deviation

• Description of Event/Issue: 3/29/19, final yield results showed 64% (vs. an average yield of 89% in FY2018)

• Evaluation participants: J. Eng (QA), L. Muench (TPL Operator), J. Ziegler & H. Chelminski (BLIP Operators), D. Medvedev (MIRP Scientist) & C. Cullen (C-AD Engineer).

• Fact Finding and Analysis (still working on it):• All other parameters in the final product spec, including Sr-

85/Sr-82, were normal; indicating no shift in beam energy.

• The target fabrication process was checked and the balance was verified with weight standards.

• Pictures of the RbCl salts show hot-spot (black color) not uniformly distributed indicating non-uniform melting (see pictures on next slide)

Pictures of High and Low yield RbCl salt targets

64% Yield 86% Yield

• Cyclotron is moving along awaiting for site office approval for low beam test, close to finalizing a schedule for commissioning

• GMP for Sr-82 well in hand, plan developed for Ac-225

• Upgrades have enhanced operations but need for additional upgrades

• Operational improvement have strengthened the program

Conclusions

Questions

Supplemental slides

Processing Rb Metal Targets at BNL

for Sr-82 Production▪ 40% increase in Sr-82 yields by using Rb metal targets compared to RbCl targets

▪ Approach: design enclosed box for inert atmosphere target opening inside hot cell

▪ Costs:

▪ Target opener fabrication and testing - $269k

▪ Granted $270k

▪ Rb metal target design and testing - $238k

▪ Granted $220k for Rb metal target development

▪ Validation of Sr-82 product from irradiated Rb metal target(s) - $373k

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MIRP Group

MIRP Group