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 product defect reporting, we have received a Pharmaceutical Quality Assurance Committee and 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 liver 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. UK Radiopharmacy Group - Newsletter – 2016 Q3 - page 1 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 radiopharmaceuticals 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 UK Radiopharmacy Group - Newsletter – 2016 Q3 - page 2 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.