5

Progress in Eliminating Highly Enriched Uranium and Remaining Obstacles

This chapter addresses the final charge of the statement of task for this study, which directs the Academies to provide

Most of the global supply of molybdenum-99 (Mo-99) for medical use is produced by irradiating targets containing highly enriched uranium (HEU) in research reactors (see Chapter 2). Following irradiation, targets are processed to recover Mo-99 and prepare it for commercial sale. The waste from target processing also contains HEU, which must be recovered, stored, and eventually disposed of. This chapter focuses on the elimination of HEU from both targets and waste.

The “others” referred to in the study charge include the following Mo-99/Tc-99m supply chain participants (see Chapter 2):

• Target suppliers: The companies that manufacture the HEU targets used for producing Mo-99.

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¹ As noted in Chapter 1, this report does not address the elimination of HEU from reactor fuel. As noted in Chapter 3, some Mo-99 is currently produced in an HEU-fueled reactor.

• Irradiation services suppliers: Operators of the research reactors used to irradiate these targets to produce Mo-99.
• Mo-99 suppliers: Companies that purchase targets, arrange for these targets to be irradiated in research reactors, and operate the facilities used to process these targets and recover Mo-99 for commercial sale.

Most of the global supply of Mo-99 is produced by five suppliers (see Chapter 3):

• Australian Nuclear Science and Technology Organisation (ANSTO), Australia
• Institut National des Radioéléments (IRE), Belgium
• Mallinckrodt, Netherlands
• Nordion, Canada
• NTP Radioisotopes (NTP), South Africa

IRE, Mallinckrot, and Nordion produce Mo-99 exclusively with HEU targets; NTP produces Mo-99 with both HEU and low enriched uranium (LEU) targets; and ANSTO produces Mo-99 exclusively with LEU targets. Chapter 3 provides additional information about these suppliers.

One current global Mo-99 supplier told the committee that global suppliers were spending between $25 million and $40 million each to eliminate HEU from Mo-99 production. The committee cannot verify this estimate because suppliers consider their conversion-related costs to be business-proprietary information.

5.1 AMERICAN MEDICAL ISOTOPES PRODUCTION ACT

The American Medical Isotopes Production Act of 2012 (P.L. 112-239) contains provisions to eliminate the use of HEU for medical isotope production and encourage the development of U.S. domestic supplies of Mo-99 and associated isotopes. Section 3174 of the Act specifies that

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² The export license cutoff date can be extended for up to 6 years if the Secretary of Energy certifies to Congress that “there is insufficient global supply of molybdenum-99 produced without the use of highly enriched uranium available to satisfy the domestic United States market; and . . . the export of United States-origin highly enriched uranium for the purposes

Three of the five current global Mo-99 suppliers (IRE, Mallinckrodt, and Nordion) use U.S.-origin HEU and are therefore subject to this provision.³ Their conversion-related activities are described later in this chapter.

Section 3173 of the 2012 Act also specifies that

The Department of Energy’s National Nuclear Security Administration (DOE-NNSA) established a technology-neutral cooperative agreement program to support domestic production of Mo-99 without HEU. It provides up to $25 million in cost sharing per agreement with potential domestic suppliers to demonstrate a capability to make at least 3,000 6-day Ci per week by 2013.⁵ As noted in Chapter 4, agreements were established initially with B&W (now BWX Technologies) and GE-Hitachi in 2009 and NorthStar Medical Radioisotopes and SHINE Medical Technologies in 2010.⁶

DOE-NNSA also signed an agreement with General Atomics (GA) in 2015 to establish production of Mo-99 in cooperation with Nordion and the University of Missouri Research Reactor Center⁷ (MURR). Mo-99 will be produced in the MURR reactor, which is currently fueled with HEU. The reactor will convert to LEU once a suitable fuel has been developed. The development of this fuel is under way and is not expected to be completed until at least 2027 (NASEM, 2016).

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of medical isotope production is the most effective temporary means to increase the supply of molybdenum-99 to the domestic United States market.”

³ NTP uses South African–origin HEU to produce Mo-99. See Chapter 3.

⁴ That is, a program that does not favor one technology or production method for Mo-99 over another.

⁵ None of the companies that established cooperative agreements with NNSA have met this capability demonstration requirement. See Chapter 4.

⁶ B&W and GE-Hitachi suspended work on these projects in 2014 and 2012, respectively. See Chapter 4.

⁷ Nordion has contracted with GA and MURR to carry out these activities.

DOE-NNSA has also established task-order agreements with IRE, Mallinckrodt, and NTP to provide resources and technical assistance for their conversion to LEU production. Additional information about these activities is provided later in this chapter.

5.2 TARGET CONVERSION

Most⁸ of the HEU targets used to produce Mo-99 for medical use have a sandwich design (see Figure 2.5 in Chapter 2). The meat of the sandwich contains uranium-aluminum alloy (UAlx)⁹ particles dispersed in aluminum alloy matrices. The meat is encapsulated in an aluminum alloy cladding that provides a barrier to the release of fission gases from the target meat and transfers heat from the meat to the reactor coolant. Targets are manufactured to meet suppliers’ particular size specifications but are typically 3-5 cm in width, 10-15 cm in length, and about 1-2 mm in thickness.

IRE, Mallinckrodt, and NTP have contracted with CERCA to develop and manufacture LEU targets having this same sandwich design, but with modifications to the target meat and cladding to accommodate LEU. Nordion has contracted with GA to develop LEU targets for producing Mo-99 at MURR. All of these target development efforts are described in the following sections.

5.2.1 IRE and Mallinckrodt

IRE and Mallinckrodt initiated the development of LEU targets in 2010. Both companies have completed their target development efforts and are receiving commercial quantities of LEU targets from CERCA. IRE plans to begin commercial production of Mo-99 from LEU targets in 2017 and to be fully converted to LEU production in 2019. Mallinckrodt plans to be fully converted to LEU targets by the end of 2017.¹⁰

A LEU target having the same design and dimensions as an HEU target would produce about 5 times less Mo-99 because it would contain less

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⁸ Nordion uses pin-type HEU targets to produce Mo-99. Use of this target will be discontinued after CNL ceases production of Mo-99 in the NRU reactor in October 2016. See Chapters 3 and 7.

⁹ UAl₂ and aluminum powder are the starting materials for dispersion targets. These materials are transformed to UAl₃/UAl₄ during the target fabrication process. The final ratio is a function of the specific processing steps employed. The resulting compound (or intermetallic compound) is referred to as “UAlx.”

¹⁰ That is, Mallinckrodt will be able to produce Mo-99 for commercial sale using LEU targets and its customers will have the necessary regulatory approvals to use this Mo-99 in technetium generators. Mallinckrodt does not expect to have a large remaining inventory of HEU targets after conversion is complete.

U-235 and more U-238.¹¹ IRE and Mallinckrodt have made two modifications to their LEU target designs to reduce this Mo-99 production penalty:

• The density of uranium in the target meat was increased to 2.6-2.8 grams uranium per cubic centimeter (gU/cc) by increasing the ratio of UAlx alloy to aluminum dispersant. (The density of uranium in the meat of a HEU target is about 1.9 gU/cc.)
• The volume of the target meat was increased by increasing its target/cladding thickness or increasing target length.

A harder aluminum alloy cladding was also used in the LEU targets to improve their manufacturability. The harder cladding minimizes distortion of the target meat during rolling operations.

Taken together, these design changes and changes in the irradiation protocol increased Mo-99 yields from LEU targets to about 80 percent of the yields from HEU targets. These companies plan to take additional steps to maintain their current Mo-99 production capacities (3,500 6-day Ci per week for Mallinckrodt and 3,600 6-day Ci per week for IRE; see Chapter 3) once they start producing with LEU targets: both companies plan to irradiate and process additional LEU targets, and Mallinckrodt also plans to irradiate targets in higher-flux positions and to increase Mo-99 recovery efficiencies.

5.2.2 NTP

NTP initiated the development of LEU targets in 2007 and began the routine commercial production of Mo-99 from these targets in June 2011. Approximately half of NTP’s processing runs in 2015 utilized LEU targets (see Chapter 3).

NTP converted from 45 percent HEU targets to 19.75 percent LEU targets, so it only had to contend with a factor of 2.5 yield penalty¹² for Mo-99 production. NTP was able to offset some of this yield penalty by increasing the density of uranium in the target meat. At that time the company chose not to make size changes to its targets to further reduce this penalty.

Mo-99 yields from NTP’s LEU targets are 20 to 25 percent lower than

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¹¹ Neutron capture losses in a LEU target are about 15 percent higher than in a comparable HEU target (Kaichao Sun and Lin-Wen Hu, MIT Nuclear Reactor Laboratory, written communication, April 28, 2016). U-238 captures neutrons to produce actinides, making fewer neutrons available for fissioning U-235 to produce Mo-99. U-238 fission can also produce Mo-99, but the thermal fission cross section for U-238 is many orders of magnitude lower than for U-235.

¹² Assuming a neutron shielding loss of about 15 percent. See Footnote 10.

yields from its HEU targets. NTP is irradiating and processing additional LEU targets to maintain its current Mo-99 production capacity of 3,000 6-day Ci per week (see Chapter 3).

5.2.3 Nordion

GA is developing a LEU target for Nordion that is radically different in design than the HEU pin targets that Nordion now uses to produce Mo-99. The target contains LEU in the form of pellets of uranium oxide encapsulated in zirconium cladding and designed to fit and be cooled within locations in the graphite reflector in the MURR reactor (see Chapter 4). The design of the target is proprietary and details were not revealed to the committee.

The target is still in development stages and has not yet been qualified for use (see Section 5.3). GA told the committee that commercial production of Mo-99 with this technology can begin in the first half of 2018 if development and licensing activities go forward as planned (see Chapter 4).

5.2.4 Other Mo-99 Suppliers

To the committee’s knowledge, the Russian Federation is the only other country besides these discussed above that uses HEU to produce Mo-99. Russian-origin HEU is currently being used to produce Mo-99 at the Karpov Institute in Obninsk and the Research Institute of Atomic Reactors (RIAR) in Dimitrovgrad (see Chapter 3).¹³ Both of these institutes produce Mo-99 by irradiating HEU targets in HEU-fueled reactors.

At present, the Russian Federation produces only enough Mo-99 for its own use and for limited export (see Chapter 3). Russia has expressed an interest in becoming a global Mo-99 supplier by expanding production at RIAR (see Chapter 3).

RIAR has carried out preliminary design work on a LEU target that it estimates could also be used to produce Mo-99. However, Russia has not made a public commitment or announced a schedule for converting its Mo-99 production to LEU targets. Such conversion would also require modifications to RIAR’s target processing facilities, which could be costly, and additional regulatory approvals in export markets to use Russian-produced Mo-99.

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¹³ Mo-99 production is under development at the Kurchatov Institute of Atomic Energy in Moscow using a LEU-fueled aqueous solution reactor (ARGUS). Production of Mo-99/Tc-99m at other Russian institutes is discussed in Zhuikov (2014).

5.3 IRRADIATION FACILITY CONVERSION

The LEU targets described above must be qualified in each reactor that will be used to produce Mo-99 for medical use. Qualification is a multistep process for ensuring that the target meets preestablished technical and regulatory specifications with respect to, for example,

• Fission density
• Heat generation in the target meat from uranium fission and other nuclear reactions
• Target meat and cladding temperatures
• Target meat and cladding mechanical stability

The qualification process requires one or more test irradiations of a prototypic target under the conditions it is likely to encounter in the reactor, followed by physical examinations to identify material or structural changes. The overall objectives of this process are to ensure that target performance meets nuclear safety requirements and to obtain the information needed to develop target irradiation specifications.

The testing plan and analysis of results must be reviewed and approved by regulatory authorities before the target is considered to be qualified for use. The time required for target qualification can vary from a few months to over a year, and the time also depends on target design and fabrication requirements, as well as the availability of reactors and post-irradiation examination facilities to carry out the necessary work.

The LEU targets developed by IRE, Mallinckrodt, and NTP are similar in design to already-qualified HEU targets; consequently they have similar performance specifications and should therefore be easier to qualify. Indeed, NTP has already qualified its LEU targets for use in the SAFARI-1 reactor and, as noted previously, is producing Mo-99 from these targets on a routine basis. IRE and Mallinckrodt have qualified their targets in all of the reactors they currently use to produce medical isotopes with HEU targets (see Chapter 3).¹⁴ However, neither of these suppliers is currently making Mo-99 for commercial sale with their LEU targets.

The LEU target being developed by GA for selective gaseous extraction has a different design than Nordion’s already-qualified HEU target. This target has not yet been qualified for use.

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¹⁴ IRE also informed the committee that it plans to qualify its LEU targets in the future for use in the LV-15 Reactor (Czech Republic) and FRM II (Germany).

5.4 PROCESSING FACILITY CONVERSION

Suppliers have made or are making changes to their processing facilities and process flow sheets to accommodate LEU targets. Those changes are described in the following sections.

5.4.1 IRE, Mallinckrodt, and NTP

IRE, Mallinckrodt, and NTP use similar aqueous chemical processes (described in Chapter 2) to dissolve HEU targets and recover Mo-99: The targets are placed in a dissolver vessel and a strong base (sodium hydroxide [NaOH]) is added to dissolve aluminum in the target meat and cladding. Uranium precipitates and is separated from the process solutions by filtering. These solutions are further processed using ion exchange and distillation to separate and purify Mo-99.

The same chemical processes can be used to recover Mo-99 from LEU targets, but some process steps must be modified to accommodate changes (described previously) in target mass and composition. Not all of these process changes were anticipated prior to cold and hot testing.

Filtering of uranium after target dissolution was a more difficult process step for LEU targets than initially anticipated. The filters were being clogged prematurely by a fine-grained precipitate, subsequently identified as magnesium hydroxide. The source of the magnesium was eventually traced to the new alloy cladding used in the LEU targets.

This filtering problem was overcome by redesigning the uranium filters and/or filtering processes to accommodate the precipitate and the higher uranium loadings associated with LEU targets. Nevertheless, some suppliers have reported to the committee that LEU filtering remains a difficult process step.

Some Mo-99 suppliers reported that the liquids from LEU target dissolution contained higher-than-expected levels of radioactive tungsten¹⁵ (tungsten-187 [W-187]). This isotope was not removed from the liquids and subsequent processing steps, so it ended up in the purified Mo-99 solutions. The source of tungsten was eventually traced to the target fabrication process used by CERCA: tungsten was introduced during TIG welding¹⁶ of the target cladding; the introduced tungsten was activated to W-187 during target irradiation. CERCA changed its fabrication process to reduce tungsten incorporation into the target.

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¹⁵ Molybdenum and tungsten are in the same chemical family and thus have similar chemical properties.

¹⁶ Tungsten inert gas welding. A tungsten electrode is used to produce the weld. The electrode is designed to be nonconsumable, but small amounts of tungsten can nevertheless be introduced into the welded material.

Neutron capture by U-238 in a LEU target produces about 50 times¹⁷ more actinides (e.g., plutonium) per 6-day Ci in LEU targets than in HEU targets. These additional actinides are removed during target processing. However, one producer (Mallinckrodt) had to develop a method to identify individual actinides and their contributions to total radioactivity in purified Mo-99 at the request of the U.S. Food and Drug Administration.¹⁸

The current status of global Mo-99 suppliers’ efforts to convert their target processing to handle LEU targets is summarized below:

• NTP processes LEU and HEU targets in different dissolver vessels but uses common hot cells for some other processing steps. (Processing equipment is replaced after each run.) NTP told the committee that it could convert entirely to Mo-99 production with LEU targets in about 8 days (the amount of time required to irradiate LEU targets in the reactor) if demand warranted.
• IRE has two sets of hot cells for producing Mo-99. It is producing Mo-99 from HEU targets in one set of hot cells while it establishes Mo-99 production from LEU targets in the other set of hot cells. IRE plans to begin producing Mo-99 with LEU targets in 2017 and to be completely converted to LEU targets by the end of 2019. The company also plans to bring a new processing facility online in the 2020s.
• Mallinckrodt also has two sets of hot cells for producing Mo-99. The company plans to begin hot testing its process for producing Mo-99 from LEU targets in one set of hot cells while it produces Mo-99 for commercial sale from HEU targets in the other set. The company plans to begin producing Mo-99 for commercial sale with LEU targets in one set of hot cells, and it plans to convert its second set of hot cells to produce Mo-99 with LEU targets once all of its HEU targets are used up.

5.4.2 Nordion

The LEU targets being developed by GA for Nordion will be processed in hot cells at MURR using selective gaseous extraction (see Chapter 4). A gas containing chlorine and oxygen will be passed through the irradiated target pellets to extract Mo-99 and some other fission isotopes. These extracted products will be transported to Nordion in Kanata, Ontario, Canada, for purification.

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¹⁷ The ratio of the U-238 atoms to U-235 atoms in LEU is ~4:1 compared to ~0.08:1 in HEU.

¹⁸ Roy Brown, Mallinckrodt, verbal communication, October 22, 2015.

The extraction process is still in developmental stages. Processing of small batches of irradiated target material has been carried out at MURR, and information from these tests is being used to refine the technology. As noted previously, full-scale testing will not take place until MURR receives regulatory approvals. These approvals are not likely before mid-2017 at the earliest.

5.5 WASTE MANAGEMENT

The production of Mo-99 by aqueous chemical processing of irradiated HEU or LEU targets produces the following four waste streams:

• Uranium solids (alkaline target dissolution only). These solids, which contain LEU or HEU, are placed into long-term storage for reuse or disposal.
• Processing off-gases, primarily the noble gases xenon (Xe-131m, Xe-133, Xe-133m, and Xe-135) and krypton (Kr-85). These gases are stored for several months to allow time for radioactive decay. Following storage, the gases are vented to the atmosphere.
• Process liquids from target dissolution. These liquids contain fission products and neutron activation products produced during target irradiation. These wastes are typically solidified and packaged for disposal.
• Other solid wastes produced during target processing: for example, radioactively contaminated processing equipment. These wastes are also packaged for disposal.

Each Mo-99 supplier has a different approach for managing these wastes, depending on the regulations and storage/disposal facilities available in host countries. Production of Mo-99 by aqueous processing of LEU targets will produce these same types of waste streams, but some waste volumes will be larger. Current global Mo-99 suppliers are developing additional capacity to manage these wastes as part of their conversion efforts.

Production of Mo-99 from GA’s selective gaseous extraction process will also produce solid and gaseous waste streams, but their compositions and volumes will likely be different than those produced by conventional aqueous processing of irradiated LEU plate targets. GA did not provide enough information to the committee to allow it to evaluate waste throughputs from its process.

Section 2.6 in Chapter 2 describes the important role that radioactive xenon (radioxenon) plays in compliance monitoring for the Comprehensive Nuclear Test Ban Treaty. The conversion of Mo-99 production from HEU to LEU targets will not change radioxenon or other off-gas production

levels; Mo-99 and radioxenon will be produced in the same relative quantities regardless of whether HEU or LEU is used. Mo-99 suppliers can reduce their radioxenon emissions if desired by increasing storage hold-up times before venting these gases to the atmosphere.

The four global Mo-99 suppliers that use HEU targets (IRE, Mallinckrodt, Nordion, NTP) will still possess large quantities of weapons-grade waste¹⁹ even after they have converted to Mo-99 production using LEU targets. These suppliers are responsible for managing this waste consistent with the laws and regulations in their host countries. The Academies (NRC, 2009) recommended that the DOE increase its focus on eliminating the HEU wastes from Mo-99 production from U.S.-origin HEU by examining options for downblending this waste or returning it to the United States. This is a potentially difficult recommendation to execute because DOE does not own this waste and cannot compel suppliers to downblend or return it to the United States.

The DOE-NNSA Office of Material Management and Minimization has two programs that are addressing this recommendation:

• The Nuclear Material Removal Program supports the return to the United States of U.S.-origin HEU that was used in targets for the production of Mo-99, provided the material meets the receiving facility criteria.
• The Gap Program can support the in-country disposition of these materials.

NNSA reported to the committee²⁰ that it is working with several countries to disposition this target residual material (TRM) and has made some progress:

• Canada has agreed to return the liquid HEU TRM that is now being stored at Canadian Nuclear Laboratories (CNL) to the United States. Shipments were scheduled to begin in the summer of 2016 and continue for about 18 months.²¹ Canada is evaluating disposition options for its solidified TRM.
• Argentina completed the in-country downblending of its HEU TRM in March 2016, and Indonesia completed in-country downblending of its HEU TRM in August 2016. This downblending was carried out with DOE’s technical and financial support.

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¹⁹ Irradiation of HEU targets for Mo-99 production typically consumes 3 percent or less of the HEU.

²⁰ Rilla Hamilton, DOE-NNSA, written communication, April 20, 2016.

²¹ These shipments had not begun as of September 1, 2016.

• DOE has consulted with Belgium about the possible return of HEU TRM to the United States. Belgium has not yet decided on a disposition pathway for this material.
• Netherlands has no plans to return its HEU TRM to the United States; its plans, if any, for downblending this waste are unclear.

Several other countries have produced Mo-99 with non-U.S.-origin HEU: Pakistan, Russian Federation, and South Africa. NNSA reported to the committee that “South Africa remains unreceptive to detailed discussions on [downblending this material].” DOE has not engaged Pakistan or the Russian Federal governments in any discussions on downblending.

5.6 ASSISTANCE FROM DOE-NNSA

As noted in Section 5.1 of this chapter, DOE-NNSA is providing financial support to some current global Mo-99 suppliers. Funding and authorization for this NNSA-supported work is provided by Congress through annual appropriations.²²

Two types of support are being provided: (1) technical assistance from U.S. national laboratories to address conversion-related issues (the contracts and work scopes for this assistance are not made public), and (2) task-order agreements administered by the U.S. national laboratories to help accelerate suppliers’ conversion efforts. Specific task orders are proposed by the suppliers and must be agreed to by the laboratory and DOE-NNSA before any government funding is provided. The technical and financial details of the agreements are proprietary; however, the committee was able to obtain general information about some of the work being carried out under these agreements from individual suppliers.

To date, NNSA has provided the following cost-shared support to the following organizations:

• IRE: $9.4M
• Mallinckrodt: $4.6M
• NTP and the South African Nuclear Energy Corporation (NECSA): $24.3M

5.6.1 IRE

IRE has received financial support to address conversion-related research and development issues and LEU target qualification.

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²² Rilla Hamilton, DOE-NNSA, written communication, June 8, 2016.

5.6.2 Mallinckrodt

Mallinckrodt has received financial support for several purposes:

• Supporting the purchase of an additional transport cask to ship irradiated LEU targets from reactors to Mallinckrodt’s processing facility in Petten, the Netherlands. This additional cask is needed to transport the larger numbers of irradiated LEU targets required to maintain current Mo-99 production capacity of 3,500 6-day Ci per week.
• LEU target testing at Mallinckrodt’s production facility in Petten.
• Technical services from Pacific Northwest National Laboratory on techniques for making alpha measurements on Mo-99 to meet regulatory requirements.
• Purchase of Mo-99 from other suppliers when one of Mallinckrodt’s hot cell lines is shut down for testing and conversion to Mo-99 production with LEU targets.

5.6.3 NTP

NTP has received financial support for the acceleration of its conversion project. The support to NECSA is being used to evaluate treatment of uranium residues and the higher volumes of waste from Mo-99 production without HEU. NECSA has subcontracted with ANSTO to complete this work because ANSTO has extensive experience with waste management techniques. NNSA has not provided any funding directly to ANSTO.

5.6.4 General Atomics

GA is one of five cooperative agreement partners with DOE-NNSA to develop domestic production of Mo-99 without HEU. DOE-NNSA is providing up to $25 million in cost sharing to GA to develop a domestic production capability in cooperation with Nordion and MURR. Mo-99 will be produced with LEU targets, as noted previously. This partnership is described in more detail in Chapter 4. To date, NNSA has provided $9.7M to GA under this agreement.

5.7 ASSISTANCE FROM OTHER ORGANIZATIONS

A number of other organizations are promoting the elimination of HEU from medical isotope production through a variety of means. Some of these efforts were discussed in previous chapters of this report. These efforts include the following:

• The U.S. Nuclear Regulatory Commission (NRC) and the Food and Drug Administration (FDA) have committed to expediting the review of license amendments and applications for the production and commercial sale of Mo-99 produced without HEU.
• The U.S. technetium generator supplier Lantheus Medical Imaging is promoting the commercial sale of LEU-sourced technetium generators²³ in North American markets. It was the first company to sell these technetium generators in the United States (the first generator sales were in 2011). Lantheus has manufactured over 95 percent of the LEU-sourced technetium generators sold in the United States since early January 2013. The company has also produced an educational video and is offering webinars to its customers on Mo-99 made without HEU.
• The Centers for Medicare & Medicaid Services (CMS) have approved a $10 add-on payment under the Hospital Outpatient Prospective Payment System for use of Tc-99m doses prepared from non-HEU sources. This payment is described in Sidebar 5.1.
• UPPI, an independently owned group of university-based nuclear pharmacies, is implementing a strategy, referred to as the UPPI LEU walk, to convert its 83 nuclear pharmacies to use Mo-99 from non-HEU sources. It is also taking action to encourage private payers to offer the $10 add-on reimbursement for Tc-99m doses prepared from non-HEU sources.
• The Veterans Administration reinforced its original mission for preferential procurement of non-HEU-based Mo-99 utilization in a March 28, 2016, memorandum addressed to the 115 Veterans Administration Medical Centers performing nuclear medicine studies.
• The White House Office of Science and Technology Policy has established the Mo-99 stakeholders working group to coordinate efforts across the U.S. government and the private sector to establish a stable domestic supply of Mo-99 for medical use and eliminate the civilian use of HEU in targets and target processing facilities used to produce Mo-99. The group holds meetings in Washington, DC, about three times per year.
• NNSA sponsors an annual Mo-99 Topical Meeting to discuss progress toward achieving non-HEU production of Mo-99 with Mo-99/Tc-99m supply chain participants and other interested parties.
• The Organisation for Economic Co-operation and Development’s Nuclear Energy Agency established a High Level Working Group on the Security of Supply of Medical Radioisotopes (HLG-MR).

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²³ At least 95 percent of the Mo-99 in these generators is made using LEU targets.

• The group is comprised of representatives from countries with interests in medical isotope production and the International Atomic Energy Agency (IAEA). The HLG-MR coordinates efforts to improve the reliability of Mo-99 supplies and to monitor conversion efforts (see Section 2.7.1 in Chapter 2).

• The IAEA convenes meetings of technical experts to discuss issues related to the elimination of HEU from medical isotope production. In October 2015, for example, the agency sponsored the technical meeting entitled Global Capabilities for the Production and Manufacture of Molybdenum-99 Targets.

The activities of these organizations serve various purposes and impact different parts of the Mo-99/Tc-99m supply chain. For example, the NRC and FDA efforts are intended to accelerate the elimination of HEU from Mo-99 production at the front end of the supply chain. The Lantheus, UPPI, and CMS efforts are intended to stimulate commercial demand for Mo-99/Tc-99m produced without HEU targets. Other activities provide further opportunities for technical exchanges and discussions on elimination of HEU in Mo-99 production and improving global Mo-99 supply reliability.

Several participating States in the 2016 Nuclear Security Summit (NSS) pledged²⁴ to make “every effort to achieve further progress with regard to minimizing and eliminating the use of highly enriched uranium (HEU) in civilian applications.” These efforts include LEU alternatives for medical isotope production:

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²⁴ NSS 2016: Gift Basket on Minimizing and Eliminating the Use of Highly Enriched Uranium in Civilian Applications. Available at http://static1.squarespace.com/static/568be36505f8e2af8023adf7/t/56febac0b654f939134d97d1/1459534530157/HEU+Minimization+Gift+Basket+for+NSS+2016.pdf.

• Ensure that any exports of HEU are done within the existing legal and regulatory frameworks and are either (1) for the sole purpose of producing needed medical isotopes or tied to a pledge from the facility receiving the HEU for demonstrated actions to convert to the use of LEU, or (2) for the specific purpose of disposition in the receiving country by blending down that material to LEU or by other secure means.

These efforts were agreed to by several States that host Mo-99/Tc-99m supply chain facilities, including Argentina, Australia, Canada, Czech Republic, Indonesia, the Netherlands, Poland, Republic of Korea, and the United States.

5.8 FINDINGS AND RECOMMENDATIONS

The HEU-export elimination provision in the American Medical Isotopes Production Act of 2012 provides strong incentives for current Mo-99 suppliers that use U.S.-origin HEU—IRE, Mallinckrodt, and Nordion—to eliminate its use from medical isotope production. NTP is not affected by this provision because it uses South African–origin HEU to produce Mo-99. Nevertheless, NTP showed early leadership by being the first global supplier to demonstrate that it is technically and commercially 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 and was the first supplier to demonstrate large-scale (>1,000 6-day Ci per week) production of Mo-99 with LEU targets.

NNSA is providing financial support and U.S. national laboratories have also provided technical support to some current global suppliers to convert to Mo-99 production using LEU targets. NNSA’s financial and technical assistance to IRE, Mallinckrodt, and NTP, described in Section 5.6 in this chapter, have helped these suppliers overcome technical chal-

lenges associated with conversion. The availability of this assistance likely accelerated the conversion schedules for these suppliers.

The committee judges that there are no insurmountable obstacles to the elimination of HEU from medical isotope production. As noted above, ANSTO and NTP have demonstrated that it is technically and economically feasible to produce Mo-99 without HEU. 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 to produce greater than 1,000 6-day Ci per week of Mo-99 for commercial sale on a routine basis.

Nevertheless, progress toward elimination of HEU from medical isotope production has been uneven:

• ANSTO has always produced Mo-99 without HEU.
• NTP converted from HEU to LEU targets over about a 5-year period (2007-2011) and now sells commercial quantities of Mo-99 produced with LEU targets.
• IRE initiated development of LEU targets in 2010 and plans to begin commercial production of Mo-99 with these targets in mid-2017, an elapsed time of about 8 years.
• Mallinckrodt initiated development of LEU targets in 2010 and plans to convert to LEU targets by the end of 2017, an elapsed time of about 8 years.
• Nordion, in cooperation with GA and MURR, initiated the development of LEU targets in late 2015 and plans to begin commercial production of Mo-99 with these targets in the first half of 2018, an elapsed time of about 2.5 years. As noted below, the committee views this schedule as optimistic.

This unevenness is primarily the result of suppliers’ commitments to conversion and their resourcefulness in overcoming the unanticipated problems that were described in Section 5.4 of this chapter.

IRE and Mallinckrodt must complete several tasks before they can begin routine commercial production of Mo-99 with LEU targets:

• Hot testing of the Mo-99 production process with LEU targets needs to be completed. This testing may reveal additional process problems that will need to be resolved. For example, both ANSTO and NTP had to make adjustments to their process flow sheets for LEU targets to raise Mo-99 separation efficiencies to levels characteristic for HEU targets (typically 80 to 90 percent).
• A dedicated LEU target processing line needs to be set up and tested in each facility.

• Full-scale Mo-99 production runs with LEU targets will need to be made to provide data for Drug Master Files²⁵; additionally, three full-scale runs will need to be made to provide Mo-99 to technetium generator suppliers for preparation of a New Drug Application (NDA) or supplemental NDA (sNDA).
• The NDA or sNDA needs to be reviewed and approved by regulatory authorities. Inspections of the Mo-99 production facilities may be carried out as part of the approval process.

The committee judges that IRE’s and Mallinckrodt’s schedules for converting to Mo-99 production with LEU targets in one of their two process lines are achievable if they do not encounter any unexpected delays in completing the steps outlined above. IRE has already encountered a several-month delay in completing the conversion of its first processing line because of the issues described in Section 5.4 of this chapter. Additional delays in completing these steps could push the start of commercial production into late 2017 or beyond.

Nordion will stop producing Mo-99 with HEU targets at the end of October 2016 (see Chapter 3) and plans to begin producing Mo-99 at MURR using LEU targets in the first half of 2018. The schedule for initial commercial production at MURR appears 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. Neither Nordion nor GA has shared detailed information about the selective gaseous extraction technology or development results. Consequently, the committee does not have sufficient information to judge whether the first-half 2018 schedule is achievable.

It is important to note that some companies will continue to produce medical isotopes in HEU-fueled reactors even after HEU is eliminated from targets and medical isotope production facilities. The reactors in Belgium (BR-2) and Missouri (MURR) have committed to conversion after suitable LEU fuel is developed. The reactors in Russia have not committed to converting to LEU fuel. See NASEM (2016) for additional information.

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²⁵ As noted in Appendix 4A in Chapter 4, a DMF is not required by law or regulation but can facilitate the regulatory approval process.

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) find themselves at a competitive disadvantage in the market; their costs for producing Mo-99 with LEU targets are higher, but their ability to increase prices to cover these costs is limited by the ready availability of Mo-99 produced with HEU targets. These companies described this situation to the committee 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 (see Section 5.7) to increase utilization. There are at least two reasons for this situation: (1) Mo-99 produced with LEU targets provides no additional medical benefits to patients; and (2) there are ready supplies of Mo-99 produced with HEU targets to meet patient needs. In fact, the global demand for Mo-99 produced with LEU targets currently is lower than global supply capacity.

Recommendation 5B is intended 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. Several actions could be taken to address this recommendation. For example:

• CMS: Continue to offer the $10 add-on per dose reimbursement for Tc-99m from non-HEU sources until Tc-99m from HEU sources is no longer available for commercial sale in the United States. At the same time, accelerate the retrospective analysis of medical procedure costs that utilize Tc-99m from non-HEU sources so that reimbursement rates more closely reflect actual Tc-99m production costs.
• NNSA: Examine options to eliminate the availability of HEU for Mo-99 production to shorten the transition period. For example, NNSA could buy 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. This would reduce and might even eliminate the transition period for global suppliers to use up their HEU target inventories. It would also reduce the volume of HEU waste resulting from the use of these target inventories.
• Technetium generator suppliers and nuclear pharmacies: Continue to work with the medical community, their purchasing organiza-

• tions, and private insurance companies to further increase the utilization of Mo-99 produced without HEU targets. UPPI’s effort to encourage private payers to offer the $10 add-on reimbursement for Mo-99 produced from non-HEU sources has the potential to further accelerate the transition away from HEU use.

• U.S. Congress: Restrict or place financial penalties on the import of Mo-99 produced with HEU targets after Mo-99 produced without HEU targets becomes widely available for commercial sale in the United States.

DOE-NNSA has taken several actions to implement the Academies’ 2009 recommendation (NRC, 2009) to manage the HEU wastes from Mo-99 production from U.S.-origin HEU. These actions are described in Section 5.5 of this chapter. 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 work with Argentina and Indonesia to downblend their HEU wastes. The HEU in waste from Mo-99 production in Pakistan, South Africa, and the Russia Federation is not U.S. origin. Nevertheless, this waste is still a proliferation hazard. Recommendation 5C is intended to further improve the management of HEU wastes to reduce their proliferation hazard.

The committee leaves it to the U.S. government to determine the best way to develop the recommended global inventory of HEU wastes. Mo-99 suppliers, their host governments, and/or the IAEA may have the information needed to develop this inventory.

To the committee’s knowledge, the Russian Federation has not made a public commitment to eliminate HEU targets from Mo-99 production or announced a schedule for doing so. Once a decision is made to convert it could take 3 years or longer before any Mo-99 is available for commercial sale. The Russian Federation has all of the necessary technical expertise to develop LEU targets and associated Mo-99 recovery and purification processes without any outside assistance. Nevertheless, efforts to convert Russian Mo-99 production to LEU targets could encounter the obstacles described in Sections 5.2-5.4 of this chapter. This report may be helpful to Russian technologists in overcoming these obstacles.

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 Mo-99 production without HEU, 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 HLG-MR 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.
• The U.S. government, again in cooperation with the HLG-MR, could examine options for discouraging sales of Mo-99 produced with HEU targets on international markets once current global

• suppliers complete their conversions to LEU targets. Such options could include policy statements and possibly even a tariff system for Mo-99 produced with HEU targets.

• The U.S. government could encourage engagements on medical isotope production between the U.S. and Russian technical communities. Such engagements could include technical exchanges that could benefit both countries and hasten Russia’s entry into global markets as a supplier of Mo-99 produced with LEU targets. Such engagements could also provide opportunities for unofficial exchanges of information and views between the U.S. and Russian governments.

Russia could become an important global supplier of Mo-99 in the future. The steps suggested above could help accelerate the entry of Russian-made Mo-99 produced with LEU targets into global markets in a responsible and sustainable manner.