The worldwide supply of 99Mo relies on a limited number of research reactors and processing facilities.
Its production is essential for nuclear medicine as 99mTc, obtained from 99Mo/99mTc generators, is used in about 80% of diagnostic nuclear imaging procedures.
These applications represent approximately 30 millionexaminations yearly worldwide.
Therefore, a weekly 99Mo production of about 9.500 Ci '6-day'calibrated is required to supply North America (53%), Europe(23%), Asia (20%) and the rest of the world (4%).
Given the short half-lives of 99Mo (66 hours) and its daughter 99mTc (6 hours), a regular supply of 99Mo/99mTc generators to hospitals or central radiopharmacies is required.
1. Introduction : The Mo-99 supply chain
99Mo/99mTc Generator
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The supply chain consists of :uranium target manufacturersnuclear reactors for target irradiationprocessing facilities to dissolve the irradiated targets and extract 99Mo99Mo/99mTc generators manufacturersradiopharmacies to elute 99mTc from the generators and prepare radiopharmaceutical doses to be injected to the patients for diagnosistransport companies to ship the produced activities to the different participants involved in the supply chain.
Carriers More carriers
Processing Facilities
Users
HospitalsNuclear Reactors
From the producers to the users … No time to lose …
1. Introduction : The Mo-99 supply chain
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Historically, there were only five nuclear reactors involved in the production of 99Mo on an industrial scale, i.e. NRU (Canada), HFR(The Netherlands), BR2 (Belgium), OSIRIS (France) and SAFARI(South Africa).They irradiated Highly Enriched Uranium (HEU) targets for the production of about 95% of the available 99Mo by four processing facilities: AECL/MDS NORDION (Canada), IRE (Belgium), COVIDIEN (The Netherlands) and NTP (South Africa). However, these ageing reactors - all of them are currently over 45 years old - are subject to unscheduled shutdowns and longer maintenance periods making the 99Mo supply chain vulnerable and unreliable. Several severe disruptions have been experienced since 2008 due to the occurrence of problems at different stages of the supply chain: reactor outages, release of activity from processing facilities, recall of 99Mo/99mTc generators by the manufacturers, …
2. The current Mo-99/Tc-99m supply situation
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Ten reactors are currently represented in the AIPES Reactors and Isotopes Working Group: NRU (Canada), BR2 (Belgium), HFR(Netherlands), OSIRIS (France), SAFARI (South Africa), MARIA (Poland), LVR-15 (Czech Republic), OPAL (Australia), RA-3 (Argentina) and FRM-II (Germany; currently not irradiating targets for Mo-99).
The estimated Mo-99 production capacities of the current irradiators are:
Six processors are currently represented in the AIPES R&I Working Group: AECL/NORDION (Canada), ANSTO (Australia), IRE (Belgium), MALLINCKRODT(NL), NTP (South Africa) and CNEA (Argentina).
The estimated Mo-99 production capacities of the current processors are:
To ensure security of supply, the AIPES R&I WG tries :to achieve the best possible coordination of the reactor operating periods to provide an optimal global coverage during planned reactor shutdown periods for refueling and maintenanceto solve problems through its Emergency Response Team (ERT)
T h F S a Su M T u W T h F Sa S u M T u W T h F Sa S u M Tu W Th F S a Su M T u W T h F S a0 1 02 03 04 05 06 07 0 8 09 10 11 12 13 14 15 16 17 18 19 20 21 22 2 3 24 25 26 27 28 29 30 31
H F R Pe ttenO S I S ac la yB R 2 M o lM AR IA O tw o ck S w ier kL VR 15 R e zS a far i P e lind a b aN R U C h alk R iv e rO P AL M e n ai
S u M T u W T h F S a Su M T u W T h F S a S u M T u W T h F Sa S u M Tu W T h F S a01 02 03 04 05 06 07 0 8 09 10 11 12 13 14 15 16 17 18 19 20 21 22 2 3 24 25 26 27 28
H F R Pe ttenO S I S ac la yB R 2 M o lM AR IA O tw o ck S w ier kL VR 15 R e zS a far i P e lind a b aN R U C h alk R iv e rO P AL M e n ai
S u M T u W T h F S a Su M T u W T h F S a S u M T u W T h F Sa S u M Tu W T h F S a S u M T u01 02 03 04 05 06 07 0 8 09 10 11 12 13 14 15 16 17 18 19 20 21 22 2 3 24 25 26 27 28 29 30 31
H F R Pe ttenO S I S ac la yB R 2 M o lM AR IA O tw o ck S w ier kL VR 15 R e zS a far i P e lind a b aN R U C h alk R iv e rO P AL M e n ai
Ja n u ar y 20 1 5
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W e e k 1 0
W e e k 7
W e ek 4 W e e k 5
F e br ua ry 2 0 15
M a rc h 2 0 1 5
W e ek 6 W e e k 8
W e e k 1 1 W e ek 12
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2. Current Mo-99 supply chain AIPES = Association of Imaging Producers & Equipment Suppliers
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Several organizations have been working together since 2008 to define measures that should be taken to secure the supply of 99Mo in the short, medium and long term :
the OECD Nuclear Energy Agency (NEA), the International Atomic Energy Agency (IAEA),the Association of Imaging Producers and Equipment Suppliers (AIPES) the European Commission (EC)the US Department of Energy (US DOE), …
The 'High Level Group' on the Security of Supply of Medical Radioisotopes (HLG-MR) has been created in April 2009 to examine the underlying reasons for the shortage and to develop a policy approach to ensure their long-termsecurity of supply.
3. Actions taken for a secure supply of Mo-99
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The HLG-MR established six principles for a long-term secure 99Mo/99mTc supply:Principle 1: All 99mTc supply chain participants should implement full-cost recovery, including costs related to capital replacement.Principle 2: Reserve capacity should be sourced and paid for by the supply chain. A common approach should be used to determine the amount of reserve capacity required.Principle 3: Recognizing the role of the market, governments should establishthe proper environment for infrastructure investment, to implement full-cost recovery methodology, …Principle 4: Given their political commitments to non-proliferation and nuclear security, governments should provide support, as appropriate, to reactors and processors to facilitate the conversion of their facilities to LEU …Principle 5: International collaboration should be continued through a policy and information sharing forum, recognizing the importance of a globally consistent approach to addressing security of supply of 99Mo/99mTc …Principle 6: There is a need for periodic review of the supply chain to verify whether 99Mo/99mTc producers are implementing full-cost recovery, whether players are implementing the other HLG-MR approaches and that operating schedules coordination has no negative effects on market operations.
NEA, "The Supply of Medical Radioisotopes: The Path to Reliability",
OECD 2011, NEA No. 6985, ISBN-978-92-64-99164-4, Paris, France.
3. Actions taken for a secure supply of Mo-99
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Several research reactors are scheduled to be shutdown within the next decade and even if some will be replaced, some critical periods are expected in 2016-2017 taking into account:
the growing 99Mo demand (0,5% per year in mature markets; 5% per year in emerging markets)the constraints on processingfacilitiesthe impact of the conversionfrom HEU to low enriched uranium (LEU) targets.
2016/2017
While the current situation looks very secure, the supply chain remains fragile and further 99Mo supply shortages could be expected in the near future.
NEA, "The Supply of Medical Radioisotopes: The Path to Reliability",
OECD 2011, NEA No. 6985, ISBN-978-92-64-99164-4, Paris, France.
3. Actions taken for a secure supply of Mo-99
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Several actions have been taken by the AIPES 'Reactors and Isotopes' Working Group in the past years to improve the Mo-99 production monitoring and provide suitable communication to stakeholders.
As a result, there were no significant supply shortages in 2014despite several reactor and processing facility events during this period.
The ERT (Emergency Response Team) has been created in 2012 within the AIPES 'Reactors and Isotopes' Working Group to follow production and supply issues – week by week – through conference calls if requested. This continuous follow-up allows to identify potential Mo-99 shortages and to define action plans with research reactors, processors and generator manufacturers, including support for ‘fresh’and ‘irradiated’ targets shipments.
3. Actions taken for a secure supply of Mo-99
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The "VERSAILLES Mo-99 MODEL" has been developed and validated by AIPES in 2014 based on data provided in the OECD/NEA (2013/2014) reports and feedback delivered by the AIPES representatives (processors and generators manufac-turers) for the years 2013 and 2014.
This model follows the global Mo-99 maximum weekly reactor production capacity – week by week – and is a suitable tool to assist scheduling the reactor operating periods with respect to an optimal security of Mo-99 production.
Especially, the "VERSAILLES Mo-99 MODEL" will help to identify periods of increased risks for Mo-99 supply shortages and to define the optimal reactor operating periods.
3. Actions taken for a secure supply of Mo-99
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It appears that the supply of Mo-99 should be sufficientduring 2015 subject to a reduced reserve capacity at reactor level (BR2 refurbishment) and lesser flexibility for rescheduling in case unscheduled events would occur in the supply chain.It should also be noticed that a reactor production capacity below the 9.500 '6-d' Ci red line during a particular week does not means that the reduced Mo-99 production capacity would result into a severe Mo-99 shortage which would not be manageable by the supply chain and impact patient treatments seriously. However, the model is able to identify periods at risk which need to be further investigated at processor and generator manufacturer level. Suitable action plans can then be defined to mitigate the impact in the supply chain in case of necessity.
3. Actions taken for a secure supply of Mo-99
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At processor level, ANSTO (Australia) is currently constructing a new processing and waste facility which is expected to start in 2016 for the supply of 3.500 ‘6-d’ Ci per week.Several risks will impact the supply chain in near future:
scheduled extended shutdown of the BR2 reactor for the replacement of its beryllium matrix (February 2015 – June 2016); this project is ‘on track’ …definitive shutdown of the OSIRIS reactor (December 2015)decision to cease routine Mo-99 production in the NRU reactor(October 2016)transition period (2016 – 2017) to enable the conversion programs from HEU into LEU targets in European research reactors and processing facilitiesentrance of new Mo-99 (Tc-99m) production sources on the market, … but which ones will be commissioned and when ?
4. Mo-99 supply issues and perspectives
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The definitive shutdown of the OSIRIS (France) reactor end of 2015 and the decision taken by the Government of Canada to cease routine Mo-99 production at the NRU (Canada) reactor end of October 2016 will result in a reduction of about 30% of the global Mo-99 production capacity by the end of 2016. Nevertheless, the Government of Canada has decided to support an extension of the NRU operations until March 31, 2018 after which the reactor will be shut down definitively. NRUwill remain fully operational to perform material testing programs and production of radioisotopes other than Mo-99 such (Co-60) but not Xe-133 which is a fission product resulting from the dissolution of targets irradiated for Mo-99 production.However, it is Canada’s intention to keep the NRU available between November 1, 2016 and March 31, 2018 as a back-upproduction capacity for Mo-99 in case of significant shortage on the market.
4. Mo-99 supply issues and perspectives
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The Belgian Nuclear Research Centre – SCK•CEN – which operates the BR2 High-Flux Reactor made a strategical decision to maintain an important multipurpose neutron source on site.
For this reason, SCK•CEN decided to proceed to the refurbishment of the BR2 Reactor – replacement of its beryllium matrix mainly – from Mid February 2015 until June 2016 (temporary shutdown of 16 months).
This major maintenance will provide a safe and reliableoperation of the BR2 reactor until 2026 to make the bridge with the projected replacement facility MYRRHA (Accelerator Driven System, ADS) scheduled to start in 2025.
MYRRHA ADS
Refurbishment of the BR2 Reactor
February 2015 June 2016
4. Mo-99 supply issues and perspectives
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SCK•CEN believes that the main production route for Mo-99 will continue to rely on the irradiation of uranium targets (converted from HEU into LEU) in research reactors.
The BR2 refurbishment period has been chosen in accordance with the ‘Global Mo-99 Supply Chain’ taking following parameters into account :
Definitive shutdown of the OSIRIS reactor at the end of 2015Stop of routine Mo-99 production at NRU from November 2016
After its refurbishment, BR2’s annual operating regime could be upgraded from 5 (before refurbishment) up to 8 operating cyclesdepending on the economics :
Before refurbishment : 120 – 140 operating days per yearIn 2016 : Restart after refurbishment, 4 to 5 operating cycles (?)From 2017 : 180 – 200 operating days per year
Refurbishment of the BR2 Reactor
February 2015 June 2016
4. Mo-99 supply issues and perspectives
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Reactor Production RoutesFission of solid LEU targets : 235U(n,fission)99MoFission of LEU in solution : 235U(n,fission)99MoNeutron capture : 98Mo(n,γ)99Mo
Accelerator Production Routes
Photofission reaction : 238U(γ,fission)99MoPhotonuclear reaction : 100Mo(γ,n)99MoPhotoneutrons generated from e- beam for fission LEU in solutionD-T neutron generators to fission LEU in solution: 235U(n,fission)99MoSpallation neutron source production (ADS) : 235U(n,fission)99MoDirect 99mTc production by cyclotron : 100Mo(p,2n)99mTc
Alternative methods for producing Mo-99 and Tc-99m without the use of HEU …
4. Mo-99 supply issues and perspectives
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The definitive shutdown of the OSIRIS (France) reactor at the end of 2015 and the decision taken by the Government of Canada to cease routine Mo-99 production at the NRU (Canada) reactor from November 1, 2016 will result in a reduction of about 30% of the current global Mo-99 production capacity by the end of 2016.
Fortunately, the BR2 (Belgium) reactor will come back into service in July 2016 for a period of at least 10 years and an increased operating regime subject to the economics.
It should be also highlighted that the processing capacityassociated to the NRU (Canada) reactor will also be lost for routine production by November 1, 2016.
The commissioning of the new processing capacity at ANSTOin 2016 is also essential to compensate for the loss of the processing capacity associated to the NRU reactor in Canada.
5. Conclusions
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The recurrent supply shortages highlighted the vulnerability of centering production on a limited number of ageing reactors and encouraged the industry to develop new projects and new production routes to increase and diversify production capacities.
Several new projects are expected to be commissioned in the period 2015 – 2020 and will help to increase and diversifyproduction capacities of Mo-99 and Tc-99m in future.
The Mo-99 production by irradiation of uranium targets in research reactors will remain the main production route in future, but there is still a lot of work to do to achieve optimal conversion from HEU to LEU targets.
5. Conclusions
Thank You For Your Attention …
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