The treatment and diagnosis of many diseases relies on a stable and secure supply of radioisotopes, yet this supply can sometimes be disrupted, as SciTech Europa explores.
Radioisotopes are used in medicine for the diagnosis and treatment of various diseases, including cancers, cardiovascular and brain disorders. Indeed, according to the European Commission, over 10,000 hospitals worldwide use radioisotopes for the in vivo diagnosis or treatment of about 35 million patients every year, of which nine million are in Europe.
‘Technetium-99m (Tc-99m) is the most widely used (diagnostic) isotope,’ the Commission says. ‘Europe is the second largest consumer of Tc-99m, accounting for more than 20% of the global market.’
This isotope – used as a radioactive tracer which can be detected in the body by medical equipment (gamma cameras) – is employed in tens of millions of medical diagnostic procedures annually.
However, as the Commission highlights, the production of Tc-99m is a complex process ‘which includes [the] irradiation of uranium targets in nuclear research reactors to produce Molybdenum-99 (Mo-99), extraction of Mo-99 from targets in specialised processing facilities, production of Tc-99m generators and shipment to hospitals. Unfortunately, the current Tc-99m supply relies on an unsustainably low number of production reactors. As those reactors were constructed in the 1950s and 1960s, they are approaching the end of their lifespan, which causes an increasing need for planned maintenance shutdowns and a growing frequency of unplanned production interruptions. As a result, the global supply of radioisotopes has become more fragile, particularly in recent years.’
Demand and supply
Indeed, this year saw Canada’s National Research Universal (NRU) – one of the largest and most versatile research reactors in the world which was responsible for the production of about 40% of global supply of Mo-99 (the precursor of Tc-99m) – permanently shut down.
NRU was built not only to supply radioisotopes but also as a major neutron physics research facility and to provide engineering research and development support for Canada’s nuclear power programme. The reactor operated at power levels up to 135 MWt and had an annual capacity factor of around 80%.
In comments carried by ‘World Nuclear News’, in a joint statement, Canadian Nuclear Laboratories President and CEO Mark Lesinski and President and CEO of Atomic Energy of Canada Limited (a Canadian federal Crown corporation and Canada’s largest nuclear science and technology laboratory) Richard Sexton said: “The contributions to science and humanity made by this reactor and the team within are immeasurable. Canada provided lifesaving medical isotopes to the benefit of over a billion people; we built and supported the continued operation of a nuclear fleet that has provided clean, reliable energy to Canada and the world; we have supported research that has led to Nobel prizes, grown our understanding of the world we live in, and enabled technological and industrial advances that we enjoy each and every day. In short, NRU and the team have made the world a better place.”
This followed a decision last year by the National Nuclear Regulator (NNR) in South Africa to direct the South African Nuclear Energy Corporation (NECSA) to cease production operations at the NTP Radiochemicals Complex and to conduct an investigation into the management of safety within the facility. This was in response to concerns emanating from NECSA’s failure to adhere to safety requirements and violations of established procedures.
However, production has since resumed, with NECSA’s subsidiary company, NTP Radioisotopes, apparently now complying with the necessary safety requirements. However, the shutdown of the facility – which lasted longer than expected – adversely affected the international supply of radioisotopes.
The RadioGenix System
In February this year, in the USA, the US Food and Drug Administration and the Nuclear Regulatory Commission (NRC) took steps to ensure a stable and secure supply of a critical radioactive imaging product used to detect potentially life-threatening diseases. The FDA approved the RadioGenix System, a unique system for producing Tc-99m imaging. The NRC is issuing guidance and will license the RadioGenix System to enable the Tc-99m it produces to be used for its medical purpose.
Dr Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said at the time: “Every day, tens of thousands of people in the US undergo a nuclear medical imaging procedure that depends on Tc-99m. This radioisotope is vital to disease detection, yet health care professionals have faced challenges with adequate supply due to a complex supply chain that sometimes resulted in shortages. Today’s approval has been the result of years of co-ordination across the FDA and with US government organisations and marks the first domestic supply of Mo-99 – the source of Tc-99m – in 30 years, which will help to ensure more reliable, clean and secure access to this important imaging agent used in nuclear medicine.”
As the regulatory authority responsible for overseeing the production, distribution, possession and use of radioactive materials and products containing radioactive materials, NRC is issuing guidance that will advise medical and commercial nuclear pharmacy users on the license amendments they will need to possess and use the RadioGenix System.
The approval was for the RadioGenix System to produce a sodium pertechnetate Tc-99m injection to be injected intravenously, instilled into the bladder or eye, or used with other FDA approved imaging drugs to examine specific tissues and organs. This approval did not require new clinical studies because it relied on safety and efficacy information and data from an already FDA-approved Tc-99m generator. The approval of RadioGenix System was granted to NorthStar Medical Radioisotopes.
Due to their short decay times, Mo-99 and Tc-99m cannot be stockpiled and must be produced continuously and delivered to hospitals weekly. Any supply disruption can lead to a situation where crucial diagnostic imaging tests must be cancelled or postponed. The Mo-99/Tc-99m supply crisis which occurred in 2009-2010 resulted in many patients having important diagnostic tests cancelled or delayed, thereby exposing the fragility of the production chain, relying on a low number of nuclear research reactors.
In Europe, the rationale for the creation of the European Observatory on the Supply of Medical Radioisotopes, which was set up in 2012, was to establish a body that can help to solve issues concerning the Mo-99/Tc-99m supply chain which directly impacts on healthcare needs.
The role of the European Observatory is thus to bring together all relevant information to the decision makers in the EU, national governments, national and international official bodies, the medical community and the European industry in order to assist them to define strategies and policies of their implementation.
The European Observatory has the following general strategic objectives:
- To support secure Mo-99/Tc-99m supply for the medium and long term, across the EU taking into account the worldwide need and supply
- To ensure that the Mo-99/Tc-99m supply issue is given high political visibility in international and national institutions, organisations and bodies
- To encourage the creation of a sustainable economic structure of the Mo-99/Tc-99m supply chain through supporting the implementation of the full-cost recovery methodology developed by OECD/NEA High-level Group on the Security of Supply of Medical Radioisotopes (HLG-MR)
- To establish periodic reviews of the Mo-99/Tc-99m supply chain and capacities, with all stakeholders across the EU, taking into account the worldwide needs and supply capacities, and to forecast future needs.
The Observatory will function through working groups on four issues:
- Global reactor scheduling and Mo-99 supply monitoring;
- Full-cost recovery mechanisms for the Mo-99 supply in compliance with OECD/NEA HLG-MR policy principles;
- Management of conversion from highly enriched uranium (HEU) to low-enriched uranium (LEU) for medical isotope production; and
- Mo-99/Tc-99m capacity and infrastructure development.
Augustin Janssens, Chairman of the Observatory’s Steering Committee, said: “It is a unique mixed panel of experts from the various competent Directorates-General of the European Commission (led by the Directorate-General for Energy), the Euratom Supply Agency, working as one team with the relevant industry experts.”
Marc Gheeraert, president of AIPES (the Association of Imaging Producers & Equipment Suppliers) and co-chairman of the Observatory’s Steering Committee, added: “The Observatory is a primeur, where European industry works hand in hand with the European Commission, the OECD/NEA and the European Association of Nuclear Medicine (EANM) for the benefit of the health of patients in Europe and across the world.”
This European project is unique and has a global reach and responsibility, which will allow faster, more accurate and safer ways to detect, enable treatment of diseases as well as monitor their evolution.
This article will appear in SciTech Europa Quarterly issue 28, which will be published in September, 2018.