NEWSLETTER U.K. Radiopharmacy G roup 2016 Q3

QUALITY ASSURANCE OF ASEPTIC PRODUCT DEFECT REPORTING PREPARATION SERVICES (QAAPS) 5TH EDITION Following the April edition of the UKRG Newsletter, Dr Alison Beaney, on behalf of the NHS highlighting the importance of adverse reaction and Pharmaceutical Quality Assurance Committee and product defect reporting, we have received a in conjunction with the Royal Pharmaceutical number of these reports. As previously stated, all Society of Great Britain, has published a new of us can play a key role reporting adverse edition of the Quality Assurance of Aseptic reactions, and product defects, but it is also Preparation Services (5th Edition). As a member of important to see the outcome of these reports. the UKRG Committee and Strategic Group, Dr Therefore, a summary of the reports received to Beaney has an excellent understanding of the date this year, is provided below: function of Radiopharmacies and has adapted current Good Manufacturing Practice Guidance Date Product Product Defect Reported from the MHRA and European Commission, into a set of standards that are applicable to all May 16 Tc99m Low Tc99m yield, normal Radiopharmacies not operating under an MHRA generator volume licence. Licensed units may also benefit from this May 16 Mertiatide Low RCP – improved with publication, which expands on current EU GMP time guidance in a manner that may be more applicable May 16 Mertiatide Low RCP: 10% free Tc99m to aseptic units, including Radiopharmacies, in the May 16 Mertiatide Low RCP: 10% free Tc99m United Kingdom. The official release from the RPS Jun 16 Mertiatide Low RCP: 10% free Tc99m is reproduced below: Jun 16 Mertiatide Low RCP: 15% free Tc99m Jun 16 Mertiatide Low RCP in 20 vials (15- The Royal Pharmaceutical Society is pleased to 50% impurities) announce that new standards for aseptic Jun 16 Mertiatide Low RCP: 17% hydrophilic preparation services are now available as part of impurity our library of professional standards and can be Jun 16 Nanocolloid Low RCP: 75-85% with 15 found on the RPS website: vials Jun 16 Mertiatide Low RCP: 15% hydrophilic http://www.rpharms.com/qaaps impurity Jul 16 Mertiatide Low RCP: 12.8% lipophilic The standards, edited by Dr Alison M Beaney, are a and 9.2% hydrophilic joint initiative between the Royal Pharmaceutical impurities. Scans showed Society and the NHS Pharmaceutical Quality uptake in and lung. Assurance Committee.These nationally-agreed Jul 16 Mertiatide Low RCP < 60% (4 kits) standards for aseptic preparation services in the UK Jul 16 Nanocolloid Uptake in kidneys and have been completely revised and include many bladder new standards. There is an increased emphasis on Aug 16 Tc99m Crack in elution vial – Pharmaceutical Quality Systems. The standards generator discovered after production are applicable to all products prepared aseptically Sep 16 Mertiatide Low RCP: 88%, in unlicensed NHS units for administration to (predominantly hydrophilic patients. The standards are the basis for regular impurities) audit of all unlicensed aseptic preparation services. A standards handbook is under development as a Remember, if you experience a product defect, it is practical text that incorporates both the standards important to report it via the BNMS website. The and additional support resources. link for error reporting is:

Further details for pre-orders of the standards www.bnms.org.uk/adverse-event/defect-reporting/ handbook are available on the above link.

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suspected. So why was it an issue now, and not ADVERSE REACTION REPORTS before?

Investigation: In addition to the product defect reports, reporting The EP standard for rubber closures is that 12 vials adverse reactions to is also a are punctured a total of four times each, and should key aspect of being part of a multi-disciplinary generate no more than five particles when their team. Since the start of this year, the following solution is run through a 50 µm filter. This is adverse reactions have been reported with the use interesting, as most radiopharmacies would of radiopharmaceuticals. consider it to be an issue if they detected five particles from 12 vials punctured only four times. Date Product Reaction Reported In any case, the generator manufacturer had Mar 16 Tetrofosmin Vomiting; redness and noticed a slight increase in the number of particles swelling of face 24hr later detected in the EP quality control tests, although Apr 16 Tetrofosmin Rash – appeared next day they were still passing. Secondly, operator technique is a factor. It was noted that our May 16 SeHCAT Anaphylaxis punctures were clustered (see pictures below) and May 16 Medronate Pruritis that the legs of the closure had been struck or Jun 16 Radium- Swelling of hands and scraped on several occasions, which is thought to 223 lower legs, causing pain be the origin of most particles. and affecting mobility

Jun 16 Datscan Vomiting. Onset 3 hrs post injection, continued for 2 days Jun 16 Tetrofosmin Extensive rash Jul 16 Ga68- Maculo-papular rash, lower Dotanoc legs, 12 hours post study Sep 16 Technegas Tingling of lips post administration

Adverse reactions to radiopharmaceuticals should be reported to BNMS on their website, using the This edition’s “Is it just me?” comes from a link Radiopharmacy in Plymouth, who asks… www.bnms.org.uk/adverse-event/defect-reporting/ “Is it just me, or is anyone else experiencing sporadic low elution yields from their Tc-99m generators?” “IS IT JUST ME?” “We went through a period where we experienced significantly reduced elution yields from around the Last month we introduced a new section of the third/fourth elution onwards on a cycle of roughly UKRG Newsletter, called “Is it just me?” once every four weeks. We did consider the “alcohol poisoning” chestnut but we still had the We had a very good response to this section, with problem when we were extra vigilant and repeated some readers writing in to register a question, and flushing elutions did not return yields to normal. some members of the UKRG Committee offering There was no correlation to operators working with some advice to help them. So, last month, you may the generators.” remember, my department started things off with the question… So if you think you can offer some advice to our reader, or you simply want to let them know that it “Is it just me, or has anyone else noticed an isn’t just them, please send an email to the editor at increase in particles (floaters) appearing in their products?” –Clint Waight, Edinburgh. [email protected]

As it turned out – it wasn’t just me! Over a period of with the title “Is it just me?” and we’ll publish the six weeks, our rate of floaters in products rose from response in the next newsletter. Also, if you have a couple per year, to approximately one per day on another “Is it just me?” for the next newsletter, average – with some days seeing up to six please send it in as above. instances. These were identified as fragments of the rubber septum of the generator elution vial, as I -Clint Waight, Editor

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BOURNVILLE WORKSHOP 2017: REGULATORY ISSUES (Remember - it’s on a Wednesday!)

Feedback from recent GMP inspections Due to availability issues at the Beeches Hotel in Bournville, the Annual Bournville Workshop will be In each issue of the newsletter, we try to let you held on a Wednesday this January. The date for know what the MHRA have found in their most the workshop is Wednesday 11th January, with the recent inspections of radiopharmacies. This might UKRG Strategic Group and the UKRG Committee help those of us with upcoming inspections to meetings happening on Monday the 9th and address these issues in advance. This month, the Tuesday the 10th of January respectively. main areas identified by inspectors as deficiencies in GMP are: Ideas for presentations & workshops 1. Chapter 8 of EU GMP - Complaints and The UKRG Committee have broadly decided on Recalls, was updated in March 2015, but potential topics for presentations and workshops, some SOPs do not reflect these changes. with a summary of the workshop listed on the last (Link to Eudralex Vol IV, Chapter 8) page of this newsletter.

2. Insufficient involvement of Quality The final line-up, including speakers, is close to being agreed, and is available on the BNMS Assurance in the investigation of deviations website, and reproduced at the end of this and change control. newsletter, along with registration forms. 3. Processes demonstrated at sites were not If you have any further ideas on what you’d like to accurately reflected in their SOPs. see at the workshop in the future, please contact your local UKRG Committee member. 4. Previous inspection findings were not addressed.

Update on EU GMP MHRA DRAFT GUIDANCE: DATA INTEGRITY DEFINITIONS AND In addition to keeping up to date with MHRA GUIDANCE FOR INDUSTRY guidance, it is a good idea to routinely check for updates on the EudraLex website at this URL: http://ec.europa.eu/health/documents/eudralex/vol-

4/index_en.htm The MHRA continue to regularly update manufacturers of medicinal products with useful Annex 16 on Certification by a Qualified Person blogs and stories relating to current GMP and Batch Release has been revised. The annex requirements and changes. An issue that many officially came into practice on the 16th of April licensed Radiopharmacies have had difficulty 2016. coming to terms with is the MHRA’s expectations regarding Data Integrity. In response to several Annex 17 on Parametric Release is being revised. “fundamental failures identified by MHRA” in recent A consultation was launched on the 15th of inspections, they have produced a draft Guidance September 2015 on a draft revised version of Document, which “is intended to be a useful Annex 17. The consultation closed on the 11th of resource on the core elements of a compliant data December 2015. governance system.”

Make sure you’ve updated your SOP on The MHRA states that the draft document provides Complaints and Recalls, as per the update to guidance on the Data Integrity expectations that Chapter 8 in March 2015! should be considered by licensed manufacturers regulated by MHRA, and should be read in conjunction with the applicable regulations and guidance on GMP. EMA REVIEW OF NEW MEDICINAL PRODUCTS It should be stressed that this is still a draft document. A link is provided below: www.gov.uk/government/news/mhra-gxp-data- The EMA publishes a monthly list of applications for integrity-definitions-and-guidance-for-industry centralised marketing authorisations for human

UK Radiopharmacy Group - Newsletter – 2016 Q3 - page 3 medicines (including radiopharmaceuticals) that are As a major global supplier of technetium-99m under evaluation by the European Medicines generators, GE Healthcare is committed to Agency's Committee for Medicinal Products for ensuring a secure, continuous and reliable supply Human Use (CHMP). of product to our customers for their diagnostic requirements. We have strong, long-term Radiopharmaceuticals appearing in this list over the partnerships in place with major reactors and key past three months include: (F18); processors in both Europe and South Africa, to Edotreotide and Lutetium (Lu177) Dotatate maintain all our global production requirements. We can therefore confirm that the NRU shutdown The full list can be found at this URL: will have no foreseeable impact on our ability to http://www.ema.europa.eu/ema/index.jsp?curl=pag deliver our generators now, or in the future. es/medicines/document_listing/document_listing_0 00349.jsp&mid=WC0b01ac05805083eb Sale of Mallinckrodt Nuclear Imaging Business

INDUSTRY NEWS On August 24th, Mallinckrodt publicly announced plans to sell their global Nuclear Imaging business to IBA Molecular. The close of the sale should UKRG Disclaimer: Much of the information in this occur in the first half of 2017, at which time all of section is proffered by UKRG Industry colleagues. Mallinckrodt’s Nuclear Medicine products, including Inclusion in the Newsletter does not imply two manufacturing plants and the majority of the endorsement of any particular product by the Nuclear Medicine staff will transfer to IBA UKRG. In addition, UKRG is not responsible for any Molecular. claims made by individual companies.

GE Healthcare’s assurance for the UPCOMING MEETINGS security of Molybdenum-99 supply in the future UKRG Annual Workshop 2017 A recent report published by the National Academy 11 January, Bournville, UK of Sciences (available at Molybdenum-99 for Website: www.ukrg.org.uk Medical Imaging | The National Academies Press) raises some concerns about a severe global 12th European Molecular Imaging Meeting medical isotope shortage (Mo99) following the 5-7 April, Cologne, Germany shutdown of the nuclear reactor at Chalk River in Website: http://www.e-smi.eu/index.php?id=2652 Canada. BNMS Annual Spring Meeting 2017 In response to this report, GE Healthcare released 20-22 May 2017, ICC, Birmingham a statement assuring their customers of their efforts to maintain a continuing supply of Mo99 despite the loss of this reactor. GE healthcare have specifically FAREWELL AND CONGRATULATIONS! asked for this assurance to be highlighted in this month’s newsletter to ensure that as many of the users of their Tc99m generators are informed as Dr Rob Smith has taken early retirement from the possible. Radiopharmacy community, and the his friends and colleagues would like to thank him for his years of The shutdown of the NRU reactor at Chalk River service and his input into the Radiopharmacy this month has been prepared for over several profession. We wish him all the best in his future. years, within the Nuclear Medicine industry in association with government and regulatory Congratulations to Chris Marshall on his recent agencies. As a result, the current irradiator and Professorship! Professor Marshall (he’ll have to get processing supply chains are in a strong position to used to being called that now), is the Director of be able to meet global demands. Wales Research and Diagnostic PET Imaging Centre at Cardiff University School of Medicine, and The Organisation for Economic Cooperation and the UKRG would like to congratulate you on this Development (OECD) Nuclear Energy Agency latest achievement. regularly monitors global demand and works in conjunction with the industry to ensure that global demand can be met. GE Healthcare has made the following assurance to their customers:

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The next meeting of the UKRG Strategic Group will From the Editor: be on January 9th, followed by the Committee meeting on the 10th and the Bournville Workshop th on the 11 (which is a Wednesday – in case you As editor of the UKRG newsletter, I often receive missed it earlier… and again later). If readers have requests from readers to be on the newsletter any issues they wish to be discussed please raise mailing list. I should point out that there is no them with your regional rep on the Committee (full mailing list for the newsletter as such, other than details at this URL): through your UKRG regional representative. http://www.bnms.org.uk/ukrg/general/ukrg- However, the newsletters are all published on the committee-list-2011.html UKRG website, so if you’re interested, please go to www.bnms.org.uk/ukrg/general/newsletters.html Alternatively, comments on the Newsletter content where you can read the entire back-catalogue if you or on any radiopharmacy issue can be sent direct to wish! the Editor at the address below.

Editor-in-Chief: Clint Waight

www.ukrg.org.uk Department of Pharmacy, The Royal Infirmary of Edinburgh, 51 Little France Crescent, UKRG Newsletter 2016 Q1 Old Dalkeith Road, Edinburgh, EH16 4SA Phone: 0131 242 2929; Fax: 0131 242 2931 Email: [email protected]

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SAVE THE DATE

The next UKRG Radiopharmacy Workshop will be held in Bournville (Birmingham) on Wednesday the 11th January 2017. Please save this date, and share with all in your region. The programme will include:

 A technical update on the status of Ga-68 radiopharmaceuticals  A clinical update on the status of Ga-68 radiopharmaceuticals  An interesting commercial update on the future of Tc-99m supply for radiopharmacies  What does the MHRA look for when inspecting radiopharmacies?  UKRG guidance on KPIs for radiopharmacy  A workshop including subjects such as “capacity planning”, “RCP testing”, “QAAPS5”

Please put this date in your diary, and join us on Wednesday 11th January 2017!

Neil Hartman [email protected]

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UK RADIOPHARMACY GROUP WORKSHOP 2017

Continuing Professional Development in Radiopharmacy Wed 11th January 2017 at The Beeches Management Centre, Bournville, Birmingham

DRAFT PROGRAMME 08:45 – Registration and Coffee 09:15 09:15 – Current status of 68Ga tracers – Speaker TBC 09:30 Technical (Maggie Cooper or Pei San Chan) 09:30 – Current status of 68Ga tracers – Speaker TBC 10:00 Clinical (? Imperial College) 10:00 – Summary of Tracia-Gay Kennedy-Dixon 10:15 adverse events Royal Liverpool Univ Hospital 10:15 – Coffee and exhibition 10:45 10:45 – What an MHRA Inspector looks for in Saima Ahmad 11:15 Radiopharmacy MHRA Inspector 11:15 – UKRG Guidance for Key David Graham 11:30 Performance Indicators (KPIs) in Aberdeen Royal Infirmary Radiopharmacy 11:30 – Industry view on the future supply of TBC 12:00 99mTc. (? Mallinckrodt – Reactor, GE – SHINE, AML – cyclotron) 12:00 – Spreadsheet to maximise the Bill Thompson 12:15 efficiency of 99Mo generator use Sandwell & W. Midlands Hospitals 12:15 – Questions and discussion about 12:30 99Mo/99mTc supply and usage 12:30 – Lunch and exhibition 14:00 14:00 – Workshops (Parallel Syndicate 15:30 Sessions) Clint Waight 1. Using the UKRG Capacity Plan Maggie Cooper 2. RCP testing Alison Beaney 3. Implementing QAAPS 5 TBC 4. TBC 15:30 – Feedback from syndicate sessions 16:00 16:00 – Summing up 16:10 16:15 Depart

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U.K. adiopharmacy roup R G UK RADIOPHARMACY GROUP WORKSHOP 2017 Continuing Professional Development in Radiopharmacy To be held on 11th January 2017 at The Beeches Management Centre, Bournville, Birmingham

BOOKING FORM Name (BLOCK CAPITALS PLEASE) Organisation Address

Phone number Fax number E-mail

I would like to book a place at the UKRG Workshop 2017 as follows: Tick if Cost required Delegate fee (to include lunch and refreshments) £100 Bed and Breakfast accommodation for the evening of 9th January 2017 £75 Bed and Breakfast accommodation for the evening of 10th January 2017 £75 TOTAL (£) PAYMENT DETAILS Payment may be made either by cheque (made payable to UK Radiopharmacy Group) or by BACS transfer (see details below)

Bank: National Westminster Sort Code: 60-02-35 Address: Birmingham City Office Account Name: UK Radiopharmacy Group 1 St Phillips Place, Account Number: 30684749 Birmingham B3 2PT BIC: NWBK GB 2L IBAN: GB05 NWBK 6002 3530 6847 49

CONDITIONS OF BOOKING: Completed Booking Forms with details of accommodation requirements, together with a cheque (or confirmation of BACS transfer) for the full amount due, should reach the organiser (see below for contact details) no later than 31st December 2016.

Those wishing to enrol later than the time specified should contact the organiser in the first instance.

In the event of cancellation, refunds will only be given if WRITTEN NOTICE reaches the organiser: - up to 28 days before the Workshop, 25% of the total fees payable will be charged - less than 28 days before the Workshop, 100% of the total fees payable will be charged (Please note, substitution of delegates will be accepted upon notification)

This booking form should be returned, together with a cheque or confirmation of BACS transfer, to the organiser:

Dr Neil Hartman Nuclear Medicine KGV Building, Basement St Bartholomew’s Hospital London EC1A 7BE In the event of any queries, please either phone 020 3465 7404 or e-mail [email protected] UK Radiopharmacy Group - Newsletter – 2016 Q3 - page 8