Congress requested that the National Academies of Sciences, Engineering, and Medicine (the Academies) conduct a study on the production and utilization of the medical isotope molybdenum-99 (Mo-99). The congressional mandate for the study is provided in the American Medical Isotopes Production Act of 2012 (AMIPA; P.L. 112-239). This summary provides the findings and recommendations from the study, organized by the five study charges in the statement of task (see Sidebar S.1).
The decay product1 of Mo-99, technetium-99m (Tc-99m), and associated2 medical isotopes iodine-131 (I-131) and xenon-133 (Xe-133) are used worldwide for medical diagnostic imaging or therapy. The United States consumes about half of the world’s supply of Mo-99, but there has been no domestic (i.e., U.S.-based) production of this isotope since the late 1980s. The United States imports Mo-99 for domestic use from Australia, Canada, Europe, and South Africa.
Mo-99 and Tc-99m cannot be stockpiled for use because of their short half-lives. Consequently, they must be routinely produced and delivered to medical imaging centers. Almost all Mo-99 for medical use is produced by irradiating highly enriched uranium (HEU) targets in research reactors, several of which are over 50 years old and are approaching the end of their operating lives. Unanticipated and extended shutdowns of some of these old reactors have resulted in severe Mo-99 supply shortages in the United
2 These isotopes are “associated” because they can be coproduced with Mo-99.
States and other countries. Some of these shortages have disrupted the delivery of medical care.
The present study examines the production and utilization of Mo-99 and associated medical isotopes, including the elimination of HEU in the reactor targets used for such production. A second Academies study examined the use of HEU in research reactor fuel. This study was completed in early 2016 and published in the report titled Reducing the Use of Highly Enriched Uranium in Civilian Research Reactors (NASEM, 2016).
The committee developed the following two findings to address this study charge (see Chapter 3):
FINDING 1A: As of June 2016, most (~95 percent) of the global supply of molybdenum-99 for medical use is produced in seven research reactors located in Australia, Canada, Europe, and South Africa and supplied from five target processing facilities in those same locations. The remainder (~5 percent) of the global supply is produced in other locations for regional use.
FINDING 1B: As of June 2016, about 75 percent of the global supply of molybdenum-99 for medical use is produced by irradiating highly enriched uranium targets in six research reactors; one of these reactors is also fueled with highly enriched uranium. The remaining 25 percent of global supply is produced by irradiating low enriched uranium targets in two research reactors.
One of the reactors used to produce Mo-99 (SAFARI-1 in South Africa) irradiates both HEU and low enriched uranium (LEU) targets. Information about these reactors and target processing facilities is provided in Tables 3.2 and 3.3 in Chapter 3.
The committee developed the following four findings to address this study charge (see Chapter 3):
FINDING 2A: New molybdenum-99 supplies have become available since 2009, and expansions in available supply capacity are planned by current and new suppliers: A supplier in Australia (Australian Nuclear Science and Technology Organisation) has entered the global supply market and plans to expand its available supply capacity; existing global suppliers in Europe (Mallinckrodt) and South Africa (NTP Radioisotopes) have initiated plans to expand their available supply capacities; and the Russian Federation plans to become a global supplier.
FINDING 2B: Reactors in France (OSIRIS) and Canada (NRU) have halted or announced plans to halt molybdenum-99 production since 2009. These shutdowns have reduced/will reduce available production capacity and reserve production capacity that could be used to cover supply shortages if they occur.
Implementation of the planned expansions by current global Mo-99 suppliers would add about 4,400 6-day Ci per week4 of available supply capacity, almost offsetting the 4,680 6-day Ci per week of available supply capacity loss when the NRU reactor in Canada stops the routine production of Mo-99 after October 2016 and permanently shuts down at the end of March 2018. About 2,400 6-day Ci per week of available production capacity was lost after the OSIRIS reactor (France) shut down in December 2015.
Argentina, Brazil, and South Korea are building new reactors to provide regional supplies of Mo-99. Russia plans to become a global supplier of Mo-99 and capture about a 20 percent share of the global market using reactors at the Research Institute of Atomic Reactors in Dimitrovgrad (additional discussion of Russian plans is provided under study charge 5).
FINDING 2C: Molybdenum-99 production and supply were disrupted unexpectedly in 2009-2010 because of prolonged unplanned reactor and target processing facility shutdowns. These shutdowns caused protracted and severe molybdenum-99 supply shortages in the United States and some other countries. Shorter supply interruptions have
4 Mo-99 is frequently priced and sold based on a quantity referred to as 6-day curie, which is the measurement of the remaining radioactivity of Mo-99 six days after the time of measurement. See Sidebar 2.3 in Chapter 2.
also occurred as a result of shorter planned and unplanned reactor and target processing facility shutdowns and transport disruptions.
FINDING 2D: Coordinated actions taken by governments, molybdenum-99 suppliers, technetium generator suppliers, technetium-99m suppliers, and others since the 2009-2010 supply shortages have improved the resilience of the global supply chain, minimized supply disruptions during unplanned reactor and processing facility shutdowns, and increased molybdenum-99/technetium-99m utilization efficiencies. Supply vulnerabilities remain, however, owing to the small number of participating organizations at some steps in the supply chain.
The 2009-2010 shortages occurred when Canada’s NRU and Europe’s HFR reactors were simultaneously shut down for extended periods. Supply interruptions also occurred in 2013 as a result of shorter planned and unplanned reactor and processing facility shutdowns. Mo-99 supply has also been interrupted frequently because of transportation denials and delays. However, these are typically resolved within hours or a few days.
Several actions have been taken since the 2009-2010 supply shortages to improve the resilience of the Mo-99/Tc-99m supply chain. These actions include the development of outage reserve capacity, coordination of reactor and target processing facility outages, enhanced communications among supply chain participants, and the creation of Mo-99 supplier alliances.
In spite of these actions, vulnerabilities still remain in some parts of the supply chain owing to the small number of participating organizations. This is particularly true for the front end of the supply chain, where one company (CERCA) provides the majority of the targets used to produce Mo-99.
The committee developed the following two findings to address this study charge (see Chapter 4):
FINDING 3A: The American Medical Isotopes Production Act of 2012 and financial support from the Department of Energy’s National
Nuclear Security Administration have stimulated private-sector efforts to establish U.S. domestic production of molybdenum-99 for medical use. However, no domestic commercial production will be established before Canada stops producing molybdenum-99 after October 2016. Potential domestic molybdenum-99 suppliers face technical, financial, regulatory, and market penetration challenges. The market challenges will likely increase after current global suppliers expand production.
DOE-NNSA has entered into cooperative agreements with five U.S.based companies to develop and demonstrate technologies for domestic production of Mo-99. Work by three companies (General Atomics,5 NorthStar Medical Radioisotopes, and SHINE Medical Technologies) continues to progress toward commercial production. Each project is intended to supply half or more of U.S. needs. None of these companies will produce any Mo-99 for commercial sale before the end of October 2016 (when Canada halts production of Mo-99). It is unlikely that substantial domestic supplies of Mo-99 will become available until 2018 and beyond.
All but one of the existing global suppliers are expanding their Mo-99 production capacities to fill the supply gap that will be created when Canada stops producing Mo-99. The expanding supply of Mo-99 to the market will put further downward pressures on prices absent increased demand, likely making it difficult for new suppliers to gain a foothold in the market.
FINDING 3B: There is currently no domestic production of iodine-131 or xenon-133, but U.S. organizations are developing the capability to produce one or both of these isotopes.
Nordion (Canada) currently supplies most of the I-131 and Xe-133 used in the United States, and Institut National des Radioéléments (IRE, Belgium) recently began supplying Xe-133 to the United States. The University of Missouri Research Reactor Center has regulatory approval to produce I-131 by irradiating tellurium targets and is currently testing its process. Other potential domestic suppliers have plans to recover I-131 and Xe-133 as part of their Mo-99 production processes.
5 General Atomics is cooperating with Nordion and the University of Missouri Research Reactor Center on this project.
Chapter 6 addresses future domestic medical needs, and Chapter 7 addresses supply adequacy. The committee interprets the term “beyond” in the study charge to mean the next 5 years (i.e., until about 2021). The committee judges that there are too many uncertainties in Mo-99 supply and demand (see Chapter 6) to look any further into the future.
The committee developed the following two findings and one recommendation to address this study charge:
FINDING 4A: Domestic demand for molybdenum-99/technetium-99m for medical use has been declining for at least a decade. The decline began well before the global molybdenum-99 supply shortages in 2009-2010 and is reflected in nuclear imaging procedures that utilize technetium-99m. The average decline in domestic molybdenum-99/technetium-99m utilization from 2009-2010 to 2014-2015 was about 25 percent, similar to the estimated decline in global molybdenum-99 demand for that same period. Some of the factors responsible for the decline in domestic demand will continue to operate into the future, making it unlikely that domestic demand will increase significantly over the next 5 years. International demand for molybdenum-99 for medical use may increase over the next 5 years primarily because of higher utilization in emerging Asian markets.
Domestic medical use of Mo-99/Tc-99m is unlikely to increase significantly over the next 5 years primarily because of changes in health care policies, reimbursement rules, and medical practices. Some of these changes will take several additional years to be fully implemented across the U.S. health care system and therefore will continue to put downward pressures on domestic demand; these pressures may not be offset by potential growth factors such as aging of the U.S. population.
FINDING 4B: Global supplies of molybdenum-99 are adequate at present to meet U.S. domestic needs. However, available supply capacity will be reduced substantially after October 2016 when the Canadian supplier shuts down, and supply capacity could be reduced further in 2017-2018 when European suppliers convert to low enriched uranium targets and the Australian supplier starts up a new target process-
ing facility, especially if these suppliers encounter conversion and/or start-up delays. The committee judges that there is a substantial (>50 percent) likelihood of severe molybdenum-99/technetium-99m supply shortages after October 2016, lasting at least until current global suppliers complete their planned capacity expansions.
RECOMMENDATION 4B: The U.S. government should continue to work with the Canadian government to ensure that there is an executable and well-communicated plan in place to restart Canadian supply of molybdenum-99 after October 2016.
The Canadian government announced that its NRU reactor at the Canadian Nuclear Laboratories (CNL) would cease the routine production of Mo-99 after October 2016. The NRU reactor and associated processing facilities at CNL would be kept on hot standby until the end of March 2018, after which time the reactor will be permanently shut down. Canada will be a “supplier of last resort” during this standby period.
The committee’s finding that there is a substantial likelihood of severe Mo-99/Tc-99m supply shortages after October 2016 is based on several factors:
- The number of irradiation services suppliers will be reduced from seven to six after NRU stops producing Mo-99. Four of the remaining suppliers use reactors that are over 50 years old (BR-2, HFR, LVR-15, and SAFARI-1), and one supplier uses a reactor that is over 40 years old (Maria). Several of the reactors used to produce Mo-99 have already had unplanned and extended outages for major repairs. There is no reason to believe that such outages will not occur in the future.
- The number of global Mo-99 suppliers will be reduced from five to four after Canada halts production. Three of these suppliers (Australian Nuclear Science and Technology Organisation [ANSTO], IRE, and Mallinckrodt) are currently making substantial modifications to their facilities or processes. The potential for unexpected supply disruptions increases any time a supplier moves to a new facility or implements a new process.
- NTP and ANSTO also rely on one reactor each (SAFARI-1 and OPAL, respectively) for all of their target irradiations. They have backup-supply agreements but no backup irradiation services suppliers. Unplanned outages of one or both of these reactors could result in supply shortages, especially if the outages extend over multiple weeks.
Recommendation 4B is intended to ensure that production capacity is available after October 2016 and before April 2018 (when NRU is on hot standby) to address severe supply shortages of Mo-99 arising from unplanned shutdowns of reactors or target processing facilities.
Chapter 5 provides the committee’s assessment of the progress made by the DOE and others to eliminate worldwide use of highly enriched uranium in reactor targets and medical isotope production facilities. The committee developed the following four findings and three recommendations to address this study charge:
FINDING 5A: The American Medical Isotopes Production Act of 2012 is accelerating the elimination of worldwide use of U.S.-origin highly enriched uranium in targets and medical isotope production facilities. There are no insurmountable obstacles to the elimination of highly enriched uranium from medical isotope production. The four global molybdenum-99 suppliers that use highly enriched uranium have committed to eliminating its use in reactor targets and medical isotope production facilities and are making uneven progress toward this goal. This progress is being facilitated by financial support from the U.S. government and technical support from U.S. national laboratories.
NTP demonstrated early global leadership by being the first global supplier to demonstrate that it is technically and economically feasible to convert its facilities to produce Mo-99 using LEU targets. NTP was following in the footsteps of ANSTO, which has always produced Mo-99 with LEU targets. IRE and Mallinckrodt plan to use the same types of LEU targets and aqueous chemical processes that are currently being used by ANSTO and NTP.
Nordion plans to begin producing Mo-99 using a new technology.
However, Nordion’s first-half 2018 schedule for initial commercial production is optimistic given the unexpected technical obstacles that frequently arise with these first-of-a-kind projects as well as the long regulatory lead times normally associated with the establishment of new Mo-99 production.
FINDING 5B: Several organizations have taken leadership roles in promoting the wider utilization of molybdenum-99 produced without the use of highly enriched uranium. However, progress is being impeded by several factors, including the continued availability of molybdenum-99 produced with highly enriched uranium targets.
RECOMMENDATION 5B: The U.S. government and others should take additional actions to promote the wider utilization of molybdenum-99 and technetium-99m produced without the use of highly enriched uranium targets.
Global Mo-99 suppliers are undergoing a protracted and difficult transition away from the use of mostly HEU targets to the exclusive use of LEU targets. Companies that are now producing Mo-99 with LEU targets (ANSTO and NTP Radioisotopes) find themselves at a competitive disadvantage in the market, a situation they describe as “unsustainable.”
Market uptake of Mo-99/Tc-99m produced from LEU targets is lagging in spite of the commendable efforts being taken by many organizations to increase utilization. At present, the global demand for Mo-99 produced with LEU targets is lower than global supply capacity. Additional steps to promote the wider utilization of Mo-99/Tc-99m produced without the use of HEU targets and hasten the elimination of HEU from the global supply chain could include the following:
- Centers for Medicare & Medicaid Services: Continue to offer the $10 add-on reimbursement for Tc-99m from non-HEU sources until Mo-99 from HEU sources is no longer available for commercial sale in the United States; accelerate the retrospective analysis of medical procedure costs that utilize Tc-99m from non-HEU sources.
- NNSA: Examine options to eliminate the availability of HEU targets for Mo-99 production to shorten the transition period, for example, by buying back U.S.-origin HEU in raw or target form from global Mo-99 suppliers once Mo-99 production with LEU targets is firmly established.
- Technetium generator manufacturers and nuclear pharmacies: Continue to work with the medical community, their purchasing orga-
nizations, and private insurance companies to further increase the utilization of Mo-99 from non-HEU sources.
- U.S. Congress: Restrict or place financial penalties on the import of Mo-99 produced with HEU targets after Mo-99 from non-HEU sources becomes widely available for commercial sale in the United States.
FINDING 5C: Even after highly enriched uranium is eliminated from molybdenum-99 production, large quantities of processing wastes containing highly enriched uranium will continue to exist at multiple global locations. This weapons-grade material is a proliferation hazard. The Department of Energy’s National Nuclear Security Administration is working with global suppliers and their governments to examine options for downblending or returning this material to the United States.
RECOMMENDATION 5C: The U.S. government should continue to work with global molybdenum suppliers and their regulators to reduce the proliferation hazard from processing waste from medical isotope production containing U.S.-origin highly enriched uranium. The U.S. government should also develop a global inventory of this waste if one does not already exist.
DOE-NNSA has taken several actions to implement the 2009 Academies’ recommendation to manage the HEU wastes from Mo-99 production from U.S.-origin HEU. These actions are described in Section 5.5 of Chapter 5. Of particular note is NNSA’s work with the Canadian government to return to the United States the HEU waste that is being stored in liquid form at CNL, as well as its work with Argentina and Indonesia to downblend their HEU wastes. The HEU waste from Mo-99 production in Pakistan, South Africa, and the Russian Federation is not of U.S. origin. Nevertheless, this waste is still a proliferation hazard.
FINDING 5D: The government of the Russian Federation has not announced a commitment or schedule for converting molybdenum-99 production from highly enriched uranium to low enriched uranium targets. The continued sale of molybdenum-99 produced with highly enriched uranium targets to international markets could disrupt progress toward full market adoption of molybdenum-99 from non-highly enriched uranium sources.
RECOMMENDATION 5D: The U.S. government—through the U.S. Department of State, the U.S. Department of Energy’s National Nuclear
Security Administration, and the U.S. scientific and technical communities—should engage with the Russian government to clarify its schedule for converting molybdenum-99 production from highly enriched uranium to low enriched uranium targets. The U.S. government should pursue opportunities for engagements between U.S. and Russian scientific and technical organizations to facilitate conversion.
The continued sale of Mo-99 produced with HEU targets to international markets from the Russian Federation or any other country could delay the full transition to non-HEU supply, continue the current market distortions in Mo-99 prices, and impact the sustainability of Mo-99 supplies over the long term.
Several steps could be taken by the U.S. government to address Recommendation 5D. The U.S. government could work through the Organisation for Economic Co-operation and Development/Nuclear Energy Agency to obtain a better understanding of Russian plans and schedules for eliminating HEU from the targets used to produce Mo-99 for sale on international markets and examine options for discouraging such sales. The U.S. government could also encourage engagements on medical isotope production between the U.S. and Russian technical communities. Such engagements could also provide opportunities for unofficial exchanges of information and views between the U.S. and Russian governments.