Molybdenum shortages cause immediate and nearby shortages / crises / concerns / worries worldwide especially for medical imaging

Molybdenum is not a mineral that hits the headlines but there are two reasons why there is concern over the metal.

By "roasting" molybdenum, producers refine raw minerals into a marketable powder or pellet, and current world capacity is about 320 million pounds per year, just sufficient to meet current world demand.

Global demand is expected to grow at 3% in the West but CIS and China (and maybe India) expect to use 10% more. This is due to ;

1. Hydroprocessing catalysts are becoming essential for crude oil.
2. Increase in nuclear reactor construction. There are known 48 nuclear reactors to be built by 2013 (not including the UK 's alleged 6) , and approximately 100 are to be built by 2020.

Reactors contain mountains of very high specification Stainlesss Steel - short falls are expected starting like ...er .. now. On September 4th The London Metal Exchange announced they will start trading cobalt and molybdenum futures next year. Prices have averaged US$30 per pound for the last 3 years but have recently edged up to US$33 a pound.

Mr Jonathan George CEO of Creston said that "Molybdenum is trading at around USD 33.85 per pound but we see it moving up into the USD 40 per pound range in 2009 because there is a stranglehold on molybdenum supply."

Medical Imaging facing immediate shortage and/or crisis

On top of this an unexpected crisis (being much downplayed) has hit nuclear medicine. Molybdenum 99 is the parent of technetium and has a half life of some 66 hours so cannot be stockpiled. This is used as a target in body imaging - injected into patients - especially for cancers, Alzheimers and Parkinson's disease.

Reactors shutdown

There are 5 reactors that can produce the stuff worldwide and last week the High Flux Reactor facility at Petten in the Netherlands went down. A spokesman for the unit's operator, NRG, said an anomaly was spotted during the inspection at the end of August's operational run, and operation in September was cancelled for checks to take place.

The other four were on scheduled shutdowns . The BR-2 reactor at the Institut des Radioelements at the Belgian Nuclear Research Centre near Charleroi (50 Km south of Brussels) is shut down for refuelling - although there has been a problem locally with the release of an Iodine isotope locally This has led to a oublic instruction not to consume local produce within a radius of 5 Km of the plant - since reduced to 3 Km. BBC PA AFP Forbes French-language Belgian newspaper Le Soir reported last Saturday that Belgian and French nuclear safety authorities had found security lapses at the lab in a joint audit in November 2007.

The Osiris unit at Saclay in France is also shut for refuelling. South Africa's Safari-1 unit has modified its operating schedule. Operator Necsa said on August 28th that Safari-1 is operating at its maximum 20 MW capacity, but it will be shut down for maintenance on 30 August. The shutdown has been put back by 12 hours, as has its restart on 4 September, to help manage tightness in isotope supply.

As a result says the Society for Nuclear Medicine (SNM), "there is a distinct possibility that worldwide production of Mo-99 could completely cease for a prolonged period, with devastating results".

"A combination of anticipated outages at other production reactors, coupled with unanticipated shutdowns, is simply devastating... Following the shutdown of Canada's Chalk River facility late last year, we simply cannot afford to sit and wait as the situation continues to worsen."

Isotopes such as Mo-99 are used in diagnostic techniques, where they are taken into the body by injection or ingestion and absorbed by certain body cells and tissues. Technicians can then track the cells' movement by the trace radioactivity the isotopes give off. The isotopes are seen as essential tools against various kinds of cancer, nervous diseases like Alzheimer's and Parkinson's and cardiac complaints.

The Chalk River plant in Canada - which supplies about half the world's medical isotope needs - was eventually reopened on government orders following safety disputes last year, but is currently undergoing a planned shutdown. It's expected to re-open this week, but reports indicate that there will still be shortages of supply due to the unexpected outage at Petten.

Paradoxically the US , due to concerns over terrorists obtaining radioactive isotopes does not produce any and is entirely dependent on imports. The High Flux Isotope Reactor (or HFIR) located at Oak Ridge National Laboratory is purely a research facility.

Threates of terrorism have as a consequence also slowed down new isotope production capacity.

"This is a serious problem," said Michael Graham, SNM President-Elect. "Now, more than ever, it is critical that the United States, along with other countries, take the lead on recommending alternatives to ensure consistent access to mission-critical isotopes, which are essential to hospitals and their ability to provide patient care.

"SNM has serious concerns about this most recent outage," said SNM President Robert W. Atcher, Ph.D., M.B.A. "A combination of anticipated outages at other production reactors, coupled with unanticipated shutdowns, is simply devastating. The impact on the patients who are in need of diagnostic tests using these radioisotopes is very serious. The United States and other countries are not prepared to adequately deal with the current situation - let alone anticipate other situations as they continue to arise. Following the shutdown of Canada's Chalk River facility late last year, we simply cannot afford to sit and wait as the situation continues to worsen," added the emerging medical technology team leader at the Los Alamos National Laboratory in New Mexico.

In a conversation in February 2008 Alexander McEwan, MD, president of the Society of Nuclear Medicine and director of oncologic imaging at the Cross Cancer Institute in Edmonton, Alberta, spokeabout last November's shutdown of a nuclear reactor in Chalk River, Ontario, and its subsequent impact on US hospitals and patients.

The United States gets its supply from two main manufacturers, Covidien and BMS (Bristol-Myers Squibb Medical Imaging). They receive it raw from the reactor from Chalk River, process it, and then it is sent to hospitals and radiopharmacies. It's a fairly complex supply chain. So if the reactor at the front of this chain breaks down, then you lose your supply of molybdenum and Technetium.

About 40% of hospitals were imaging at 50%. Because Covidien gets some of its supply from Europe, it was able to supply European molybdenum. Pharmacies that BMS supplied were the ones that were hit the hardest.

In the United States, there are about 19 million imaging facilities a year using molybdenum, so about a million and a half facilities use it per month. (in the US alone)

The Society of Nuclear Medicine has identified for 10 years that this is a problem. There is no US supplier of Technetium, and we as a society are working very hard to get a US reactor into supply. But obviously, that is expensive.

Suppliers of medical molybdenum 99 isotopes meet

Following the shutdowns of the isotope reactor HFR, Netherlands, and the IRE production site, Belgium, both providing Molybdenum (Mo99), the Association of Imaging and Production Equipment Suppliers ( AIPES )organized a meeting on September 3rd in Brussels, assembling all stakeholders, from reactor operators to physicians, represented through the EANM, to ensure isotope delivery and minimize patient discomfort.

Although the Canadian and South African reactors are maximizing their output and after evaluating all alternative solutions, there will still be a shortage in delivery of Tc99 in Europe for 4 to 6 weeks.

Technetium (Tc99), end product of the Mo99, is used for tumor detection, myocardial infarct evaluation, to investigate brain diseases and other pathologies.

The reduction in Tc99 delivery could be up to 30% and will likely be evenly spread across the European nuclear medicine centers.

AIPES and EANM are currently working on recommendations for the nuclear medicine physicians on replacement isotopes readily available for certain types of examinations, which would thus permit to lessen the impact of the shortage on patients.


Due to their sensitivity and specificity, radio-isotopes labeled molecules are used in nuclear medicine for:

1. Diagnostic imaging in oncology (smallest lesion detection), cardiology, neurology and many other types of pathologies.
2. Therapy with some type of cancers and pain relief.
3. As tracers for Molecular Healthcare applications and research in latest healthcare technologies.

Despite the efforts made to overcome this temporary shortage, a long term strategy to replace the very old isotope reactors needs to be implemented at EU level as amtter of urgency.

AIPES had already started an independent assessment of future isotope needs and required production capacity which will be presented to all stakeholders upon its completion in the coming months.

........... and what is the betting that the price of M099 canisters has gone up ? It hasnt hit the TV screens yet - but it will.

UPDATE :
Saturday am Independent "Global shortage of isotopes puts hundreds of cancer scans in doubt"..."Professor Alan Perkins, honorary secretary of the British Nuclear Medicine Society, said: "The expected number of people who will be affected is quite difficult to determine ... but we are certainly talking about hundreds. The procedures include cardiac blood-flow imaging, bone scanning for secondary tumours, lymph-node detection in breast cancer cases and renal function monitoring, which is commonly done in children"

With deadpan insousiance the spokesman for the Department of Health said: "Trusts will be working to ensure that patient care is not compromised. Urgent patients will continue to be prioritised [but] routine patients may need to wait a little longer until supply comes back online."

Scotsman - Cancer scan delay fears over isotope shortages

Telegraph - Patients 'facing scan delays because of radiation shortage'

PA - Hundreds facing scan delays - which is evidently the source of the above 3 stories and the other 147 Google produces.

NHS decide on vaccine from UK based GSK - Cervarix® for teenage girls for cervical cancer causing HPV virus - genital warts ignored - none for boys

An editorial published in the BMJ on Friday ,claims (the editorial is by Jane J Kim, assistant professor of health decision science Program in Health Decision Science, Department of Health Policy and Management, Harvard School of Public Health, Boston, MA 02115, USA) that the UK government may save 18.6 million pounds ($37 million) annually as a result of its decision to select GlaxoSmithKline's ( a UK based pharma company) cervical cancer vaccine Cervarix for its human papillomavirus immunisation programme rather than Merck & Co.'s (a US basd pharma company) and Sanofi-Aventis' ( a Paris, France based company) Gardasil. (Search this site on "Gardasil" for post on the subject)

This decision is based on a study Economic evaluation of human papillomavirus vaccination in the United Kingdom by Mark Jit, Yoon Hong Choi, and W John Edmunds, Modelling and Economics Unit, Centre for Infections, Health Protection Agency, London NW9 6BT

The model involves 34 variables (Table 1) about which assumptions are made as rationally as possible on the available evidence (We then generated parameter values for cost and utility weights by Monte Carlo sampling (using the Latin hypercube method) from the joint distribution of plausible ranges of values for each parameter - which sounds impresive but is in reality a sort of re-inforced guess, as so litle actual evidence of use is currently available). To make a detailed evaluation of the methodolgy and the evidence supporting the assumptions is skilled and complicated task. Such modelling can easily be "tweaked" ... "We constructed a total of 2700 possible scenarios " . A stricture used is that users of such Monte Carlo simulations rely entirely on the initial subjective estimates and almost never follow up with empirical observation.i.e they place over reliance on the model.. which they have to because no more empirical evidence is available currently.

Faced with a need to make a decsion within a timeframe these limitations must be accepted - however we have the luxury of time, a delay in decsion making makes the position no worse and affords time to refine procedures, undertake critical analysis and consult other viewpoints.

"Only the 72% of model structures that best fit prevalence data for human papillomavirus were used in the analysis, but care should be taken when interpreting model results not to assume that each of the remaining model structures is equally plausible. etc., etc., caveat, caveat ...."

"Although we have included the estimated impact of screening in the model and tried to account for the accuracy of screening in our results, some of the details of the programme (such as rescreening women more often after a suspect result) are difficult to properly implement in the current model structure."

The conclusion arrived at was that Vaccinating 12 year old schoolgirls with a quadrivalent (protection against 4 known HPV virus' 2 of which cause genital warts) vaccine at 80% coverage is likely to be cost effective at a willingness to pay threshold of £30 000 ( Euros 37 700; $59 163) per QALY gained (quality adjusted life years (QALYs), discounted costs and benefits at 3.5% per year in the base case, and adopted a healthcare provider perspective on costs, as required by the National Institute for Health and Clinical Excellence), if the average duration of protection from the vaccine is more than 10 years.

Implementing a catch-up campaign of girls up to age 18 is likely to be cost effective.

Vaccination of boys is unlikely to be cost effective.

A bivalent vaccine (affording protection against HPV virus' that cause cervical cancer NOT genital warts) with the same efficacy against human papillomavirus types 16 and 18 costing £13-£21 less per dose (this is max. 10% of vaccine costs) (depending on the duration of vaccine protection) may be as cost effective as the quadrivalent vaccine although less effective as it does not prevent anogenital warts

Jane Kim in the editorial said that "the decision to select the bivalent vaccine implies the Department of Health is willing to accept foregone health benefits (and additional cost savings) from averting cases of genital warts for the reduced financial outlay."

Jane Kim added: "Assuming 80-percent coverage of current 12-year-old girls (each year cohort has some 350,000 girls) in the UK with the full three-dose vaccine series, this price differential translates to savings of 11.5 million pounds ($23 million) to 18.6 million pounds ($37 million) from the vaccine price alone in the first year of the programme.”

In response, a spokesperson for the Department of Health noted that "the contract has been awarded for the vaccine that scored best overall against a number of pre-agreed criteria and offers best value overall to the NHS."

This policy of limited protection at a reduced costs is not without its critics. Colm O'Mahony, a consultant in sexual health at Chester Foundation Trust, commented that “all the clinical evidence pointed to Gardasil and instead [the government has] chosen a vaccine suitable for the Third World.”

Natika Halil, director of information at the Family Planning Association, remarked that "genital warts has its own financial cost to the NHS which spends 22 million pounds ($44 million) a year treating it, so it will be interesting to see how this has been factored into the cost analysis.”

As part of the cost analysis it was intersting to note that the NHS accept that the basic pap smear at Pap smear (£21.70, 2002 prices) is less than the recently introduced liquid based cytology (£25.40, 2003 prices). Also Costs for screening at sexual health clinics and outpatient clinics are higher (£37 and £68 respectively, 2003 prices). These costs will not diappear because screening will still be required because the vaccine only affords protection against 70% of potential HPV strains.

GlaxoSmithKline stated that data on Cervarix have demonstrated the prevention of pre-cancerous lesions and a strong immune response for 6.4 years, noting that “this is the longest duration of protection reported for any vaccine against HPV 16 and 18.”

The government's vaccination programme in 12-year-old girls is expected to start in September.

The Department of Health has released Press release today "300,000 more girls to be offered vaccine against Cervical cancer - extension of the HPV vaccination progamme ". This trumpets the decision to choose Cervarix at a lower cost - for a routine vaccination of girls 12-13 years old starting in September which it is claimed will eventually save up to 400 lives for each year of girls receiving the vaccine. As a consequence The national vaccination programme against HPV is being extended to offer protection to an additional 300,000 girls aged 17-18, starting in September.

A 2 year ‘catch-up programme’ will start in the school year 2009/10 to vaccinate girls aged between 15 to 18. Today’s announcement means that girls, who would not otherwise have been included in this catch-up programme, will now be vaccinated this school year. Boys will not be vaccinated at any age.

Dawn Primarolo says the cost of the vaccine is commercially confidential. Cervarix® will be purchased by the Department of Health who will supply it free of charge to the NHS.

The financial consequences will be that The Department of Health will provide additional support to PCTs in guidance and funding to ensure that the roll out of the older cohort is a success.

There will be an additional £10 million for PCTs in the 2008/09 financial year to implement this extra programme.

It is not accidental or incidental that programme on Channel 4 Dispatches (in the UK only), "The Jab that can stop Cancer" presented by Jane Moore (who has paid privately for the vaccine for one of her daughters and will eventually for the younger daughter to have Gardasil) will discuss this subject at 8.pm this evening.

Professor David Salisbury , Director of Immunisation,Dept. of Health made great claims for the precision of the modelling and calculation for costs and benefits - making asinine remarks about the amount of computer time spent in running the models - all weekend, when nobody else was using it - as if that was proof of veracity or accuracy.

A lady epidemiologist pointed out that cervical cancer rates and mortality had fallen dramatically since pap screening was introduced and that 40 wome died per million. She queried whether the costs justified he claimed benefits say against the people who will suffer heat diseases or more common life threatening cancers.

A snapshot was also provided how the UK market was softened u by intensive (and dubious) marketing programs, and thiny veiled surveys paid for by the pharma companies were presented to the press as "evidence".

GP's , now used a better educated and better informed patient were asking for protection for their children- simply assuming the benefits it provided on the wave of "astro-turfing" or the unquestioning and incurious wall to wall press coverage.

No mention was made of the details of the modelling, nor was it made clear that Cervarix provides no protection against other HPV strains ( are over 100 known strains) that cause genital warts - nor was the case examined for protecting boys.

In the world of private medicine, Jane Moore has made her decision , US and French (and those in 100 countries where it is currently approved) citizens will make theirs (although different insurers have different policies)

NHS Choice HPV vaccination information site

How does a parent decide ?

As the NHS / Government have made a decision to supply at no extra cost the parent has to first consider ;
1. Any vaccine carries risks when used, what are those risks ?

To date the only large scale usage has been in the US and we posted about the latest report here Tuesday, July 08, 2008 Gardasil® gets 7,802 adverse reports to CDC by VAERS system

2. Having accepted that risk , what risk is there of my daughter eventually coming in contact with a strain of HPV ?

It is not 100% but near it. The more promiscuous (ie the greater number of sexual partners - of either sex, it can be transmitted between women) she is, the greater the chance. There is no clear evidence that sexually transmitted infections (STI) have any effect on increasing / reducing the impact. Please note that the cervical smear test, whilst it will may discover evidence of STI's , that information in the UK will not be passed on to the patient. It is not a genito urinary test. (As an aside it would be a service to women to re-jig the test to incorportate a genito - urinary test)

The "pap" smear testing will continue (remember that results vary regionally, and are reported differently, the NI method of identification is different to the rest of the UK. The report also identiffies that fact that over time it will be necessary ..." to take account of possible changes to the cervical screening programme, such as the introduction of DNA testing for human papillomavirus, .....It is clear that significant further work on the design of optimal screening and vaccination programmes is required, particularly if the introduction of vaccination accelerates the recent trend for the declining uptake of screening.

i.e it is possible (many would say highly likely) that vaccination will lead to lack of detection in the population as women will think or assure themselves that the unpleasant cervical smear routine can be avoided.

The FDA says the human papillomavirus is the most common sexually transmitted infection in the U.S. The Centers for Disease Control and Prevention estimates that about 6.2 million Americans become infected with genital HPV each year and that more than half of all sexually active men and women become infected at some time in their lives.

3. If she contracts an HPV will it be oncogenic (cause cervical cancer) ?

Currently it is felt that the 2 strains afforded protection by both current vaccines accounts for 75-80% of HPV's discovered in pap tests.

Of women conracting oncogenic lesions, the eventual death rate some 40 per 1 Mn a year die, many of course suffer an unpleasant and debilitating illnes for varying periods like all cancers.

4. Will better vaccines become available affording more protection ... ?

No doubt other manufacturers are working , and GSK and Merck will be improving their product - it must be assumed newer products will afford better protection and less risk at lower cost. The timescale is unknown.

To be effective protection must be given prior to any sexual contact - it is not necessary for intercourse to take place for transmission.

This site does not give medical advice, it gives plenty of information and directs the user to sources of further information. Anyone considering having their children vaccinated for HPV must consult their GP.

Joe Moore chose it for her children.

Lord Patel is ;

1. Very sceptical of the need to make a decision - there is no urgency.

2. Not at all impressed by Dr David Sainsbury Salisbury and his fancy modelling - truly it is as good as modern techniques and the data available can provide. The assumptions / guesses used are not based on sufficiently strong evidence .. yet, more will become available as others users / providers take part in a very large experiment on their children. Lord Patel can see no reason why anyone should enter their children in this great experiment. Giving you children a healthy diet, exercise and making sure they never smoke are far greater benefits you can pass on to your kids.

3. Feels that the NHS has higher priorities than providing at zero cost a protection which in essence will stimulate promiscuity rather than restrict it - with the attendant risks of STI's.

4. Is certain that undue pressure (without any proof, but based on wide experience of big pharma) has been put on the decision makers to support a "British" product.

5. It also represents another example of the state usurping personal choices and decisions using a decision making process which is opaque to many people - inlcuding most of the medical profession. (next time you see your GP ask him about the Monte Carlo method usng tjhe latin hypercube method)