2019 blip/rrpl isotope program biennial science and … · 2019-04-16 · qa in fy2018 • all...
TRANSCRIPT
1
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)
2
Target basket
Brookhaven Linac Isotope Producer (BLIP)
BLIP schematics
3
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
0
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
5
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
6
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
8
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
16
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 ($40k):
• Covered pistol grip conversion for all installed
manipulators
• Better ergonomics - great feedback from operators
• FY2017: 6 conversions, purchase 1 Model 7
manipulator
• FY2018: 6 conversions
Old style grips
Pistol grips
Ac-225 target opener
▪ Based on LANL design
• Painted floor in TPL and scrubber room
• Improved waste removal process
• Improved acid scrubber trunks
• Sr-82 hot plate controller improvement
• 2-57A is an alpha lab
• Hand and foot monitor
• HpGe detectors
• Set up more alpha probes
Target Processing Lab Upgrades
• Refurbished HB2, 3, 4 and 5 for Sr-82, research, and industrial isotope
production
• Decontaminated, repainted & lined with plastic
• Installed all new new water line and valve, acid scrubber enclosure and trunk,
manipulator boots and jaws, laboratory parts
• Cu-67 to be processed in HB3 - currently a low natural Cu environment
20
Hot Box Refurbishments
20Before After
PLC Hotplate
for Sr-82 Processing▪ Reduces risk to program
▪ Minimizes handling and spill potential
▪ PLC controlled temperature with
thermocouple feedback minimizes
potential for release to ventilation
system
▪ Grounded for electrical safety
▪ Cost effective
▪ Off-the-shelf ceramic hot plate
▪ Electronics are outside hot box to
prolong longevity
▪ Better ergonomics
▪ Reduces the need to change hot-
plates every 2 processes
Remaining TPL Upgrades
Spac
eItem
Cost
($)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
35
MIRP Group
MIRP Group