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Published on 17 September 2009

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Current concerns in radiopharmacy

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To ensure that the current supply problems facing radiopharmacy do not affect patients too greatly we need to work closely together with the manufacturers and our colleagues

The current main issue facing the hospital radiopharmacist is the purchase and supply of radiopharmaceuticals. The UK Radiopharmacy group (UKRG) and the NHS Pharmacy QA Committee have recently published a document entitled “Responsibilities of chief pharmacists for the purchase and supply of radiopharmaceuticals”.[1] This was to clarify the position of chief pharmacists and their responsibility.

Within the UK there are three ways radiopharmaceuticals are prepared for use within hospitals.
1. When manufacture takes place in specials’ licensed nonpharmacy-run departments with no pharmacy input.
2. When preparation takes place in Section 10 exemption units run under the supervision of a pharmacist.
3. When nuclear medicine departments receive multidose vials from outside radiopharmacies and draw up the doses themselves.

The system of specials is unique to the UK, in which preparations without a marketing authorisation may be prepared and sold provided the preparation facility is licensed with the licensing authority, the Medicines and Healthcare Products Regulatory agency (MHRA).

Radiopharmaceuticals are usually comprised of two components: the radioactive part, usually technetium for diagnostic imaging produced from a molybdenum/technetium generator (a licensed product), and the carrier or kit (a licensed product) specific for the area of the body to be imaged, which is combined with the technetium to produce the radiopharmaceutical, which is unlicensed. Due to the chemical bonding of the technetium to the kit a new chemical entity is formed.

For the UK, the Standards for Better Healthcare[2] drawn up by the Healthcare Commission require trusts to ensure patient safety through the safe and secure handling of medicines. For the above examples the following therefore applies.

For the case of a nonpharmacy-run specials’ licensed unit the chief pharmacist would be responsible for ensuring there are formal contracts defining responsibilities and standards. The chief pharmacist would monitor standards by ensuring any copies of audits by the licensing authority and other organisations, such as the British Nuclear Medicine Society (BNMS), are available for his/her inspection and they can reassure themselves and the hospital management of conformity to standards and Good Manufacturing Practice (GMP).

A unit operating under a section 10 exception under the Medicines Act 1968 is one run by or under the supervision of a pharmacist. Consequently the pharmacist will usually be under the management of the chief pharmacist either directly or indirectly. In this scenario the chief pharmacist would ensure the compliance to local and national standards and ensure the facility is audited to the recommendations within EL(97)52.

Finally, where a hospital has no facilities to prepare radiopharmaceuticals in house there is no option but to purchase doses in either a multidose vial, from which patient doses may be withdrawn immediately prior to administration, or purchase patient-ready doses in syringes for administration.

The chief pharmacist should ensure there is a written contract between the supplier and the department, and there are written protocols in place for the use of the products, to ensure that products are used in accordance with the licensed indications as laid out in the SPC. If products are used for unlicensed indications there must be clear documented evidence that the hospital management are aware of these uses and a risk assessment has been carried out.

Hospital radiopharmacies currently supply technetium-labelled radiopharmaceuticals to enable approximately 28 million procedures worldwide. Technetium, the daughter isotope from the decay of molybdenum, is used in 80% of nuclear medicine procedures and has a critical role in the diagnosis of heart disease, oncology and a wide range of other conditions.

The supply of radiopharmaceuticals is currently the hot topic in radiopharmacy due to supply problems of the raw material for the process, molybdenum, which began in August 2008, due to unforeseen problems at the HFR reactor which kept it offline for approximately six months.

Molybdenum is produced in five dedicated nuclear reactors around the world:

  • NRU in Canada, age 51.
  • HFR Petten Netherlands, age 47.
  • BR2 Belgium, age 47.
  • CEA Osiris France, age 42.
  • NTP Safari South Africa, age 43.

These supply 95% of the world’s demand, and although there is capacity at each reactor an emergency shutdown of one of them will cause a global shortage in the short term, and also the reactors must shut down for routine planned maintenance and refuelling. If these shutdowns coincide with an emergency
shutdown then there is no avoiding a global shortage.

The supply of molybdenum has been interrupted four times from 1997 to 2007, but there have been six disruptions since January 2007 and a further known supply problem due on October 2009, when it is possible four out of the five reactors may be closed.

To put the reactor production schedules in perspective, the two main reactors, NRU and HFR, operate for approximately 270 days per year, and there are longterm plans to maintain supplies:

Three reactors in the USA , Argentina and Australia may be able to increase production. However, due to the distances involved in the transportation of the finished isotope to the UK and Europe, this may not be a viable option. There are plans for a new reactor in France and two currently in concept in Belgium and the Netherlands.

Measures radiopharmacists can take to alleviate the problems of supply are as follows.

1.
Planning in the long term
The majority of radiopharmacies operate in isolators contained within cleanrooms. These isolators are usually modified to hold molybdenum/technetium generators by the incorporation of lead shielding to give operator protection.

Each manufacturer of generators has their own generator design and they are not identical. Consequently in times of shortage it is not possible to switch to another manufacturer quickly without having the isolator modified.

It is possible to purchase a generic isolator to store any manufacturer’s generators and if large enough able to hold more than you currently store to enable longer usage. In the case of my institution we were able to store six generators from two different suppliers with ease.

The majority of radiopharmacies usually have one molybdenum/technetium generator delivered weekly for their needs. In our case we made the decision to have three delivered on separate days each week from two manufacturers. In the times of shortage it was possible to continue to supply our customers as each manufacturer of generators had supply problems on different days/weeks.

2. Planning short term

Each of our customers was contacted on a daily and weekly basis to give predictions of the yield from the generators and their allocation of activity based on their usual usage. Each customer then decided how best to use the available activity in a way that benefited their particular need.

With the fluctuations in supply, some units on days of predicted high yield ordered large quantities, and staff within nuclear medicine departments worked a longer day (and on days of reduced activity worked shorter days).

3. Cooperation between radiopharmacies

Usually each radiopharmacy operates on its own and supplies either its own base or hospital or, in our case, four other hospitals and four veterinary surgeries. With the shortages we were able to supply our excess technetium to another department for their use.

Transport was arranged using our licensed courier company, so enabling another radiopharmacy to continue to operate at a reduced service.

4. Cooperation at department level.

With the fluctuation in supply the communication between our own nuclear medicine department and the radiopharmacy department increased and patients were booked for imaging with the available activity. Consequently our waiting lists did not grow appreciable.

5. Increased collaboration

There needs to be increased collaboration between producers to ensure the fair distribution of available isotope globally.

6. Better communication

There needs to be a better communication network established, certainly within the UK, to warn of or communicate problems.

Finally, the crisis is not over, as has been seen by the shortages of the week beginning 01.06.09 which caught half of the UK and Europe off guard. These shortages are going to be a regular event as we are relying on technology which is at least 45 years old and due for replacement.

All we can do is work together with the manufacturers and our colleagues to ensure these supply problems do not affect patients too greatly.

References
1. Responsibilities of chief pharmacists for the purchase and supply of radiopharmaceuticals. www.bnmsonline.co.uk/dmdocumentsukrg_purchase_responsibilities_
2009.pdf
2. Standards for better health. http://www.dh.gov.uk/assetRoot/04/08/66/66/04086666.pdf



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