Diagnostic companies continue to seek out new sources of Molybdenum 99 (Mo 99) to produce Technetium 99m (Tc 99m), a vital medical isotope most widely used in nuclear medicine diagnostic procedures, in response to a global shortage from repeated, unplanned outages at facilities where it currently is produced.
The latest development in response to this critical shortage of the Tc 99m isotope is an agreement between Covidien (Mansfield, Massachusetts) and the Institute of Atomic Energy in Poland (IAE POLATOM; Warsaw, Poland) to augment and further diversify Covidien's supply of Mo 99 to produce Tc 99m.
Tc 99m is used in more than 80% of all nuclear medicine diagnostic and functional studies of organs and anatomical systems, Covidien noted. Adding IAE POLATOM's Maria Research Reactor to Covidien's global supply chain is expected to help the company meet the needs of more than 1 million additional patients in just the first six months after the reactor begins supplying Mo 99, Covidien said.
"This is an historic agreement. It is the first time in decades that a new reactor has been brought into the global supply chain for medical isotopes," said Timothy Wright, president of Pharmaceuticals at Covidien. "We are excited that we will now be working together to provide more than a million patients around the globe with access to a critical medical isotope during this serious shortage."
The announcement of this agreement comes just two days before the High Flux Reactor (HFR) in Petten, the Netherlands, is scheduled to begin a six-month shutdown for scheduled repairs. The remaining operating reactors supplying Covidien are the BR2 reactor in Belgium, the Osiris reactor in France and the Safari reactor in South Africa. Canada's National Research Universal (NRU) reactor has been shut down for repairs since last May. When operating, the HFR and NRU reactors have typically provided nearly 65% of the world's supply of medical isotopes.
The Maria Research Reactor first operated from 1975 until 1985 when it was taken off line for a complete redesign. It resumed normal operations in 1993. Maria is considered to be a relatively new reactor, compared with the other five aging reactors that supply most of the world's medical isotopes, Covidien noted.
The company said the announcement of this agreement is the culmination of more than six months' collaboration between Covidien and IAE POLATOM. Processing of Mo 99 produced during a test irradiation at the Maria Research Reactor last week is currently underway at Covidien's Petten facility. Tc 99m derived from the Mo 99 produced in Poland should be commercially available to help meet European needs within 30 days. FDA approval is pending for use in the U.S. and from Health Canada for use in Canada, the company noted.
Covidien said that until approval is received in the U.S. and Canada its overall available Mo 99 will be equitably distributed globally shifting supply from current sources when needed so all regions may share the benefit of this new reactor source as the company has done throughout this situation.
"We are pleased to be cooperating with Covidien to use the scientific advancements we have made here at the Institute of Atomic Energy and the Maria Research Reactor to meet the healthcare needs of patients throughout the world at such a critical time," said Prof. Krzysztof Wieteska, director of IAE POLATOM.
Covidien said that completing this agreement required "significant technical engagement, investment and cooperation" between the company and IAE POLATOM. It also required the acquisition of more than 20 licenses and permits from multiple regulatory agencies in five European nations, the company said.
The agreement is the most recent example of steps Covidien has taken to address the current medical isotope shortage. Since early last year, the company says it has:
• Actively supported additional Mo 99 production cycles and an increase in the number of targets at Belgium's BR2 reactor during the shutdown of the HFR in the Netherlands.
• Increased the production of potential alternative, clinically appropriate medical isotopes, such as thallium Tl 201.
• Communicated frequently and directly with nuclear medicine providers about the supply challenge, providing detailed monthly calendars projecting the availability of Tc 99m generators on a daily basis.
• Published these calendars and supply updates on a public website: www.covidien.com/Mo99supply.
• Encouraged clinicians to be more efficient in scheduling procedures and ordering Tc 99m – based products to maximize the number of doses available to the greatest number of patients.
Covidien is not the only company that has worked to address the isotope shortage. Earlier this year GE Hitachi Nuclear Energy (GEH; Wilmington, North Carolina) said it had been selected by the U.S. Department of Energy's National Nuclear Security Administration (NNSA) to help develop a U.S. supply of a radioisotope. NNSA said it chose GEH to help create a reliable U.S. supply of Mo 99 without the use of HEU to respond to the shortage (Medical Device Daily, Jan. 26, 2010).
Lantheus Medical Imaging (North Billerica, Massachusetts) also has made efforts in the past year or to address the concern. In May Lantheus signed an agreement with NTP Radioisotopes, a subsidiary of the South African Nuclear Energy Corporation (both Pretoria, South Africa), to make and supply Lantheus with an ongoing volume of Mo 99 (MDD, May 22, 2009).
Lantheus also reported last year that FDA and Health Canada have approved its supplement applications to qualify the Australian Nuclear Science and Technology Organization (ANSTO) as a valid supplier for low-enriched uranium (LEU)-derived Mo 99 in the U.S. and Canada. Lantheus noted at that time that there are only a few major worldwide suppliers of Mo 99, and most use HEU targets. With these approvals, the company said it would become the first domestic company to offer Tc 99m using Mo 99 derived from LEU targets to the U.S. and Canada (MDD, July 10, 2009).
In June, the Centers for Medicare & Medicaid Services said it was considering a pathway for coverage of Sodium Fluoride (Na F-18) for PET bone imaging as an alternative to Tc 99m. Because of the severity of the isotope supply crisis, CMS has opened the PET National Coverage Determination (NCD) to evaluate the effectiveness of the NaF-18 for PET bone imaging, a nuclear medicine procedure that is sensitive for the detection of the spread of many common cancers – including breast, lung and prostate – to the bone (MDD, June 18, 2009).
"The medical community is in crisis right now," Robert Atcher, PhD, president of the Society of Nuclear Medicine (Reston, Virginia) said at that time. "Physicians can't get access to essential isotopes for common nuclear medicine procedures. As a consequence, patients are being denied tests, or have to be diagnosed with procedures that involve more radiation dose, less accuracy, more cost or more invasive techniques."
"This agreement with the IAE POLATOM will help us meet our short- and long-term needs for Molybdenum 99," Wright said. "We look forward to a productive relationship for the benefit of patients around the world."
According to Covidien, this is not the first time there has been a Mo 99 shortage. During the past four years, different reactors have been offline unexpectedly for extended periods of time, creating Mo 99 shortages. Routine maintenance shutdowns, however, are coordinated well in advance and generally do not create shortages, the company said.
Covidien noted that the additional Mo 99 from Maria would not completely offset the combined shutdowns of the HFR and NRU reactors. The company says its efforts also continue toward maximizing Mo 99 supply arrangements from all viable sources. However, the supply produced by Maria will be especially helpful, the company said, to ease certain periods of extreme isotope shortage that is anticipated when some of the other operating reactors are unavailable.
Amanda Pedersen, 229-471-4212;