Elsinga, Philip H.

Gillings, Nicholas M.

English

University of Groningen

   University of GroningenSpotlight onGillings, Nicholas M.; Elsinga, Philip H.Published in:Clinical and Translational ImagingDOI:10.1007/s40336-021-00437-wIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2021Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Gillings, N. M., & Elsinga, P. H. (2021). Spotlight on: guideline on current good radiopharmacy practice(cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacyand Chemistry (2021)6:8. Clinical and Translational Imaging, 6(8), 281–282.https://doi.org/10.1007/s40336-021-00437-wCopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 20-11-2022Vol.:(0123456789) Clinical and Translational Imaging https://doi.org/10.1007/s40336-021-00437-wSPOTLIGHTSpotlight on: guideline on current good radiopharmacy practice (cGRPP) for the small‑scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8Nicholas M. Gillings1 · Philip H. Elsinga2Received: 19 April 2021 / Accepted: 21 May 2021 © Italian Association of Nuclear Medicine and Molecular Imaging 2021Radiopharmaceuticals play a central role in nuclear medi-cine imaging. Their binding properties and pharmacokinet-ics are a major determinant of the obtained PET or SPECT image.Since radiopharmaceuticals are considered as medicines, their preparation is subject to the same legislation as for other drugs. One of the requirements is the application of Good Manufacturing Practice (GMP) which in the European Union is described in Eudralex Volume 4—Good Manufac-turing Practice Guidelines.Radiopharmaceuticals are either produced by industry or in hospitals. Industrially produced radiopharmaceuticals are often on a relatively large scale and are shipped to hospitals according to demand. Therefore, in this case, companies apply full GMP as they have sufficient resources to comply with GMP guidelines.In hospitals, radiopharmaceuticals are often prepared on a much smaller scale and are used locally for only a few patients. Usually, these radiopharmaceuticals contain short-lived radionuclides locally produced using a cyclotron or eluted from a generator. Moreover, the commercial interest for such tracers is often limited and they are therefore not commercially available. The combination of the specific characteristics of locally small-scale prepared radiophar-maceuticals with the fact that in hospitals resources is much less compared to industry makes full compliance with regu-lar GMP guidelines very challenging.Therefore, the EANM Radiopharmacy committee has developed a set of guidelines for the small-scale prepara-tion of radiopharmaceuticals according to current good radi-opharmacy practice (cGRPP). With this set of guidelines, EANM offers hospital radiopharmacies guidance on how to ensure high-quality standards appropriate to the specific conditions for the small-scale preparation of radiopharma-ceuticals (SSRP).The recently published guideline is an update of the previously published guidance [2] and also refers to other documents that have since been published by the EANM: Guidance on cGRPP for SSRPs using automated modules: a European perspective [1], Guidelines on the labeling of leucocytes with 99mTc-HMPAO [8], EANM guideline on the validation of analytical methods for radiopharmaceuticals [4], and Guidance on validation and qualification of pro-cesses and operations involving radiopharmaceuticals [7]. Furthermore, this guideline refers to the current legislative documents issues by the European Union [3], Pharmaceuti-cal Inspection Co-operation Scheme (PICs) [6], and IAEA [5].The guideline provides a useful point of reference for hospital radiopharmacies, bringing together several docu-ments published during the last 10 years to aid in the in establishment of quality standards for production of their radiopharmaceuticals. The guideline is in three parts: Part 1 contains general guidance with respect to quality assur-ance, personnel, premises, equipment, documentation, production, quality control and outsourced activities which applies for all diagnostic and therapeutic radiopharmaceu-ticlas. Part 2 contains guidance on the preparation of radi-opharmaceuticals from licensed components (generators, radionuclide precursors and kits). Part 3 contains detailed guidance on the preparation of radiopharmaceuticals from non-licensed components, including the production of  * Philip H. Elsinga  p.h.elsinga@umcg.nl Nicholas M. Gillings  nicholas.mathew.gillings@regionh.dk1 PET & Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark2 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, The Netherlands Clinical and Translational Imaging1 3PET-radiopharmaceuticals from cyclotron-produced radi-onuclides using synthesis modules and other specialized equipment.The following topics are addressed:In part 1, the use of a risk-management approach in the quality assurance (QA) system is emphasized. Fur-thermore, the requirement of having a responsible person for radiopharmaceuticals (RPR) is promoted, whereas in the general EU GMP guidelines, a qualified person (QP) is mentioned. It must be highlighted here that the require-ment for certification of radiopharmaceuticals by a QP is dependent on the type of product and applicable national legislation. Furthermore, the importance of having systems for handling deviations, changes, out of specification results (OOS) and corrective and preventative actions (CAPA) is stressed. Regarding personnel, it is described that sufficient staff must be available who have appropriate education and training. This can be offered by EANM/ESMIT at different levels, from e-learning to postgraduate courses and advanced courses. It is also stressed that, for outsourced activities, such as cleaning, monitoring, tests and qualification, written contracts should be in place.Overall, in part 1, it is described how a high level of quality assurance can be maintained in a small hospital radiopharmacy.In part 2, which covers preparation from licensed compo-nents, the following topics are explicitly described: premises and equipment, production, and quality control.For production of SSRPs from non-licensed components, as described in Part 3, a dedicated quality management system is recommended. Furthermore, besides the RPR, a separate production manager and quality control manager should ideally be available. For these radiopharmaceuticals, automated synthesis systems are often used. Conditions for the use of such systems along with validation of production processes are described. Specifically mentioned are biobur-den tests and identification of critical steps that can affect microbiology. Vendor qualification is discussed and it is rec-ommended to perform supplier audits. EANM has taken the initiative to organize joint audits under the SASAI initiative.In conclusion, the newly published guideline offers a comprehensive and up-to-date overview with reference to other applicable publications, and gives practical advice for hospital radiopharmacies with respect to the small-scale preparation of radiopharmaceuticals.Funding No funding was obtained.Declarations Conflict of interest The authors declare no competing financial inter-ests. Nic Gillings is first author of the spotlighted article and is member of the EANM Radiopharmacy Committee. Philip Elsinga is co-author of the spotlighted article and Editor-in-Chief of European Journal of Nuclear Medicine and Molecular Imaging Radiopharmacy and Chem-istry.Consent for publication All authors gave their consent for publication.References 1. Aerts J, Ballinger JR, Behe M, Decristoforo C, Elsinga PH, Faivre-Chauvet A, Mindt TL, KolencPeitl P, Todde S, Koziorowski J (2014) Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Labelled Compd Radiopharm 57:615–620 2. Elsinga P, Todde S, Penuelas I, Meyer G, Farstad B, Faivre-Chau-vet A, Mikolajczak R, Westera G, Gmeiner-Stopar T, Decristo-foro C (2010) Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 37(5):1049–1062 3. EU GMP, Volume 4 Good manufacturing practice (GMP) Guide-lines. https:// ec. europa. eu/ health/ docum ents/ eudra lex/ vol-4_ en. Accessed 30 Apr 2020 4. Gillings N, Todde S, Behe M, Decristoforo C, Elsinga P, Ferrari V, Hjelstuen O, KolencPeitl P, Koziorowski J, Laverman P, Mindt TL, Ocak M, Patt M (2020) EANM guideline on the validation of analytical methods for radiopharmaceuticals EJNMMI radiophar-macy and chemistry. EJNMMI Radiopharm Chem 5:7 5. IAEA Operational Guidance on Hospital Radiopharmacy (2008) https:// www. iaea. org/ publi catio ns/ 7708/ opera tional- guida nce- on- hospi tal- radio pharm acy 6. PIC/S Guide to good practices for the preparation of medicinal products in healthcare establishments. Version PE 010–4, March 2014. https:// www. picsc heme. org/ en/ publi catio ns. Accessed 30 Apr 2020 7. Todde S, KolencPeitl P, Elsinga P, Koziorowski J, Ferrari V, Ocak EM, Hjelstuen O, Patt M, Mindt TL, Behe M (2017) Guidance on validation and qualification of processes and operations involving radiopharmaceuticals. EJNMMI Radiopharm Chem 2:8 8. de Vries EJF, Roca M, Jamar F, Israel O, Signore A (2010) Guide-lines for the labelling of leucocytes with 99mTc-HMPAO. Eur J Nucl Med Mol Imaging 37:842–848Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Spotlight on:guideline on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8

ARTS repository - University of Groningen

   University of GroningenSpotlight onGillings, Nicholas M.; Elsinga, Philip H.Published in:Clinical and Translational ImagingDOI:10.1007/s40336-021-00437-wIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2021Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Gillings, N. M., & Elsinga, P. H. (2021). Spotlight on: guideline on current good radiopharmacy practice(cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacyand Chemistry (2021)6:8. Clinical and Translational Imaging, 6(8), 281–282. Advance online publication.https://doi.org/10.1007/s40336-021-00437-wCopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 10-09-2023Vol.:(0123456789) Clinical and Translational Imaging https://doi.org/10.1007/s40336-021-00437-wSPOTLIGHTSpotlight on: guideline on current good radiopharmacy practice (cGRPP) for the small‑scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8Nicholas M. Gillings1 · Philip H. Elsinga2Received: 19 April 2021 / Accepted: 21 May 2021 © Italian Association of Nuclear Medicine and Molecular Imaging 2021Radiopharmaceuticals play a central role in nuclear medi-cine imaging. Their binding properties and pharmacokinet-ics are a major determinant of the obtained PET or SPECT image.Since radiopharmaceuticals are considered as medicines, their preparation is subject to the same legislation as for other drugs. One of the requirements is the application of Good Manufacturing Practice (GMP) which in the European Union is described in Eudralex Volume 4—Good Manufac-turing Practice Guidelines.Radiopharmaceuticals are either produced by industry or in hospitals. Industrially produced radiopharmaceuticals are often on a relatively large scale and are shipped to hospitals according to demand. Therefore, in this case, companies apply full GMP as they have sufficient resources to comply with GMP guidelines.In hospitals, radiopharmaceuticals are often prepared on a much smaller scale and are used locally for only a few patients. Usually, these radiopharmaceuticals contain short-lived radionuclides locally produced using a cyclotron or eluted from a generator. Moreover, the commercial interest for such tracers is often limited and they are therefore not commercially available. The combination of the specific characteristics of locally small-scale prepared radiophar-maceuticals with the fact that in hospitals resources is much less compared to industry makes full compliance with regu-lar GMP guidelines very challenging.Therefore, the EANM Radiopharmacy committee has developed a set of guidelines for the small-scale prepara-tion of radiopharmaceuticals according to current good radi-opharmacy practice (cGRPP). With this set of guidelines, EANM offers hospital radiopharmacies guidance on how to ensure high-quality standards appropriate to the specific conditions for the small-scale preparation of radiopharma-ceuticals (SSRP).The recently published guideline is an update of the previously published guidance [2] and also refers to other documents that have since been published by the EANM: Guidance on cGRPP for SSRPs using automated modules: a European perspective [1], Guidelines on the labeling of leucocytes with 99mTc-HMPAO [8], EANM guideline on the validation of analytical methods for radiopharmaceuticals [4], and Guidance on validation and qualification of pro-cesses and operations involving radiopharmaceuticals [7]. Furthermore, this guideline refers to the current legislative documents issues by the European Union [3], Pharmaceuti-cal Inspection Co-operation Scheme (PICs) [6], and IAEA [5].The guideline provides a useful point of reference for hospital radiopharmacies, bringing together several docu-ments published during the last 10 years to aid in the in establishment of quality standards for production of their radiopharmaceuticals. The guideline is in three parts: Part 1 contains general guidance with respect to quality assur-ance, personnel, premises, equipment, documentation, production, quality control and outsourced activities which applies for all diagnostic and therapeutic radiopharmaceu-ticlas. Part 2 contains guidance on the preparation of radi-opharmaceuticals from licensed components (generators, radionuclide precursors and kits). Part 3 contains detailed guidance on the preparation of radiopharmaceuticals from non-licensed components, including the production of  * Philip H. Elsinga  p.h.elsinga@umcg.nl Nicholas M. Gillings  nicholas.mathew.gillings@regionh.dk1 PET & Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark2 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, The Netherlands Clinical and Translational Imaging1 3PET-radiopharmaceuticals from cyclotron-produced radi-onuclides using synthesis modules and other specialized equipment.The following topics are addressed:In part 1, the use of a risk-management approach in the quality assurance (QA) system is emphasized. Fur-thermore, the requirement of having a responsible person for radiopharmaceuticals (RPR) is promoted, whereas in the general EU GMP guidelines, a qualified person (QP) is mentioned. It must be highlighted here that the require-ment for certification of radiopharmaceuticals by a QP is dependent on the type of product and applicable national legislation. Furthermore, the importance of having systems for handling deviations, changes, out of specification results (OOS) and corrective and preventative actions (CAPA) is stressed. Regarding personnel, it is described that sufficient staff must be available who have appropriate education and training. This can be offered by EANM/ESMIT at different levels, from e-learning to postgraduate courses and advanced courses. It is also stressed that, for outsourced activities, such as cleaning, monitoring, tests and qualification, written contracts should be in place.Overall, in part 1, it is described how a high level of quality assurance can be maintained in a small hospital radiopharmacy.In part 2, which covers preparation from licensed compo-nents, the following topics are explicitly described: premises and equipment, production, and quality control.For production of SSRPs from non-licensed components, as described in Part 3, a dedicated quality management system is recommended. Furthermore, besides the RPR, a separate production manager and quality control manager should ideally be available. For these radiopharmaceuticals, automated synthesis systems are often used. Conditions for the use of such systems along with validation of production processes are described. Specifically mentioned are biobur-den tests and identification of critical steps that can affect microbiology. Vendor qualification is discussed and it is rec-ommended to perform supplier audits. EANM has taken the initiative to organize joint audits under the SASAI initiative.In conclusion, the newly published guideline offers a comprehensive and up-to-date overview with reference to other applicable publications, and gives practical advice for hospital radiopharmacies with respect to the small-scale preparation of radiopharmaceuticals.Funding No funding was obtained.Declarations Conflict of interest The authors declare no competing financial inter-ests. Nic Gillings is first author of the spotlighted article and is member of the EANM Radiopharmacy Committee. Philip Elsinga is co-author of the spotlighted article and Editor-in-Chief of European Journal of Nuclear Medicine and Molecular Imaging Radiopharmacy and Chem-istry.Consent for publication All authors gave their consent for publication.References 1. Aerts J, Ballinger JR, Behe M, Decristoforo C, Elsinga PH, Faivre-Chauvet A, Mindt TL, KolencPeitl P, Todde S, Koziorowski J (2014) Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Labelled Compd Radiopharm 57:615–620 2. Elsinga P, Todde S, Penuelas I, Meyer G, Farstad B, Faivre-Chau-vet A, Mikolajczak R, Westera G, Gmeiner-Stopar T, Decristo-foro C (2010) Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 37(5):1049–1062 3. EU GMP, Volume 4 Good manufacturing practice (GMP) Guide-lines. https:// ec. europa. eu/ health/ docum ents/ eudra lex/ vol-4_ en. Accessed 30 Apr 2020 4. Gillings N, Todde S, Behe M, Decristoforo C, Elsinga P, Ferrari V, Hjelstuen O, KolencPeitl P, Koziorowski J, Laverman P, Mindt TL, Ocak M, Patt M (2020) EANM guideline on the validation of analytical methods for radiopharmaceuticals EJNMMI radiophar-macy and chemistry. EJNMMI Radiopharm Chem 5:7 5. IAEA Operational Guidance on Hospital Radiopharmacy (2008) https:// www. iaea. org/ publi catio ns/ 7708/ opera tional- guida nce- on- hospi tal- radio pharm acy 6. PIC/S Guide to good practices for the preparation of medicinal products in healthcare establishments. Version PE 010–4, March 2014. https:// www. picsc heme. org/ en/ publi catio ns. Accessed 30 Apr 2020 7. Todde S, KolencPeitl P, Elsinga P, Koziorowski J, Ferrari V, Ocak EM, Hjelstuen O, Patt M, Mindt TL, Behe M (2017) Guidance on validation and qualification of processes and operations involving radiopharmaceuticals. EJNMMI Radiopharm Chem 2:8 8. de Vries EJF, Roca M, Jamar F, Israel O, Signore A (2010) Guide-lines for the labelling of leucocytes with 99mTc-HMPAO. Eur J Nucl Med Mol Imaging 37:842–848Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

   University of GroningenSpotlight onGillings, Nicholas M.; Elsinga, Philip H.Published in:Clinical and Translational ImagingDOI:10.1007/s40336-021-00437-wIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2021Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Gillings, N. M., & Elsinga, P. H. (2021). Spotlight on: guideline on current good radiopharmacy practice(cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacyand Chemistry (2021)6:8. Clinical and Translational Imaging, 6(8), 281–282.https://doi.org/10.1007/s40336-021-00437-wCopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 08-06-2022Vol.:(0123456789) Clinical and Translational Imaging https://doi.org/10.1007/s40336-021-00437-wSPOTLIGHTSpotlight on: guideline on current good radiopharmacy practice (cGRPP) for the small‑scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8Nicholas M. Gillings1 · Philip H. Elsinga2Received: 19 April 2021 / Accepted: 21 May 2021 © Italian Association of Nuclear Medicine and Molecular Imaging 2021Radiopharmaceuticals play a central role in nuclear medi-cine imaging. Their binding properties and pharmacokinet-ics are a major determinant of the obtained PET or SPECT image.Since radiopharmaceuticals are considered as medicines, their preparation is subject to the same legislation as for other drugs. One of the requirements is the application of Good Manufacturing Practice (GMP) which in the European Union is described in Eudralex Volume 4—Good Manufac-turing Practice Guidelines.Radiopharmaceuticals are either produced by industry or in hospitals. Industrially produced radiopharmaceuticals are often on a relatively large scale and are shipped to hospitals according to demand. Therefore, in this case, companies apply full GMP as they have sufficient resources to comply with GMP guidelines.In hospitals, radiopharmaceuticals are often prepared on a much smaller scale and are used locally for only a few patients. Usually, these radiopharmaceuticals contain short-lived radionuclides locally produced using a cyclotron or eluted from a generator. Moreover, the commercial interest for such tracers is often limited and they are therefore not commercially available. The combination of the specific characteristics of locally small-scale prepared radiophar-maceuticals with the fact that in hospitals resources is much less compared to industry makes full compliance with regu-lar GMP guidelines very challenging.Therefore, the EANM Radiopharmacy committee has developed a set of guidelines for the small-scale prepara-tion of radiopharmaceuticals according to current good radi-opharmacy practice (cGRPP). With this set of guidelines, EANM offers hospital radiopharmacies guidance on how to ensure high-quality standards appropriate to the specific conditions for the small-scale preparation of radiopharma-ceuticals (SSRP).The recently published guideline is an update of the previously published guidance [2] and also refers to other documents that have since been published by the EANM: Guidance on cGRPP for SSRPs using automated modules: a European perspective [1], Guidelines on the labeling of leucocytes with 99mTc-HMPAO [8], EANM guideline on the validation of analytical methods for radiopharmaceuticals [4], and Guidance on validation and qualification of pro-cesses and operations involving radiopharmaceuticals [7]. Furthermore, this guideline refers to the current legislative documents issues by the European Union [3], Pharmaceuti-cal Inspection Co-operation Scheme (PICs) [6], and IAEA [5].The guideline provides a useful point of reference for hospital radiopharmacies, bringing together several docu-ments published during the last 10 years to aid in the in establishment of quality standards for production of their radiopharmaceuticals. The guideline is in three parts: Part 1 contains general guidance with respect to quality assur-ance, personnel, premises, equipment, documentation, production, quality control and outsourced activities which applies for all diagnostic and therapeutic radiopharmaceu-ticlas. Part 2 contains guidance on the preparation of radi-opharmaceuticals from licensed components (generators, radionuclide precursors and kits). Part 3 contains detailed guidance on the preparation of radiopharmaceuticals from non-licensed components, including the production of  * Philip H. Elsinga  p.h.elsinga@umcg.nl Nicholas M. Gillings  nicholas.mathew.gillings@regionh.dk1 PET & Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark2 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, The Netherlands Clinical and Translational Imaging1 3PET-radiopharmaceuticals from cyclotron-produced radi-onuclides using synthesis modules and other specialized equipment.The following topics are addressed:In part 1, the use of a risk-management approach in the quality assurance (QA) system is emphasized. Fur-thermore, the requirement of having a responsible person for radiopharmaceuticals (RPR) is promoted, whereas in the general EU GMP guidelines, a qualified person (QP) is mentioned. It must be highlighted here that the require-ment for certification of radiopharmaceuticals by a QP is dependent on the type of product and applicable national legislation. Furthermore, the importance of having systems for handling deviations, changes, out of specification results (OOS) and corrective and preventative actions (CAPA) is stressed. Regarding personnel, it is described that sufficient staff must be available who have appropriate education and training. This can be offered by EANM/ESMIT at different levels, from e-learning to postgraduate courses and advanced courses. It is also stressed that, for outsourced activities, such as cleaning, monitoring, tests and qualification, written contracts should be in place.Overall, in part 1, it is described how a high level of quality assurance can be maintained in a small hospital radiopharmacy.In part 2, which covers preparation from licensed compo-nents, the following topics are explicitly described: premises and equipment, production, and quality control.For production of SSRPs from non-licensed components, as described in Part 3, a dedicated quality management system is recommended. Furthermore, besides the RPR, a separate production manager and quality control manager should ideally be available. For these radiopharmaceuticals, automated synthesis systems are often used. Conditions for the use of such systems along with validation of production processes are described. Specifically mentioned are biobur-den tests and identification of critical steps that can affect microbiology. Vendor qualification is discussed and it is rec-ommended to perform supplier audits. EANM has taken the initiative to organize joint audits under the SASAI initiative.In conclusion, the newly published guideline offers a comprehensive and up-to-date overview with reference to other applicable publications, and gives practical advice for hospital radiopharmacies with respect to the small-scale preparation of radiopharmaceuticals.Funding No funding was obtained.Declarations Conflict of interest The authors declare no competing financial inter-ests. Nic Gillings is first author of the spotlighted article and is member of the EANM Radiopharmacy Committee. Philip Elsinga is co-author of the spotlighted article and Editor-in-Chief of European Journal of Nuclear Medicine and Molecular Imaging Radiopharmacy and Chem-istry.Consent for publication All authors gave their consent for publication.References 1. Aerts J, Ballinger JR, Behe M, Decristoforo C, Elsinga PH, Faivre-Chauvet A, Mindt TL, KolencPeitl P, Todde S, Koziorowski J (2014) Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Labelled Compd Radiopharm 57:615–620 2. Elsinga P, Todde S, Penuelas I, Meyer G, Farstad B, Faivre-Chau-vet A, Mikolajczak R, Westera G, Gmeiner-Stopar T, Decristo-foro C (2010) Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 37(5):1049–1062 3. EU GMP, Volume 4 Good manufacturing practice (GMP) Guide-lines. https:// ec. europa. eu/ health/ docum ents/ eudra lex/ vol-4_ en. Accessed 30 Apr 2020 4. Gillings N, Todde S, Behe M, Decristoforo C, Elsinga P, Ferrari V, Hjelstuen O, KolencPeitl P, Koziorowski J, Laverman P, Mindt TL, Ocak M, Patt M (2020) EANM guideline on the validation of analytical methods for radiopharmaceuticals EJNMMI radiophar-macy and chemistry. EJNMMI Radiopharm Chem 5:7 5. IAEA Operational Guidance on Hospital Radiopharmacy (2008) https:// www. iaea. org/ publi catio ns/ 7708/ opera tional- guida nce- on- hospi tal- radio pharm acy 6. PIC/S Guide to good practices for the preparation of medicinal products in healthcare establishments. Version PE 010–4, March 2014. https:// www. picsc heme. org/ en/ publi catio ns. Accessed 30 Apr 2020 7. Todde S, KolencPeitl P, Elsinga P, Koziorowski J, Ferrari V, Ocak EM, Hjelstuen O, Patt M, Mindt TL, Behe M (2017) Guidance on validation and qualification of processes and operations involving radiopharmaceuticals. EJNMMI Radiopharm Chem 2:8 8. de Vries EJF, Roca M, Jamar F, Israel O, Signore A (2010) Guide-lines for the labelling of leucocytes with 99mTc-HMPAO. Eur J Nucl Med Mol Imaging 37:842–848Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Proceedings - University of Groningen

   University of GroningenSpotlight onGillings, Nicholas M.; Elsinga, Philip H.Published in:Clinical and Translational ImagingDOI:10.1007/s40336-021-00437-wIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2021Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Gillings, N. M., & Elsinga, P. H. (2021). Spotlight on: guideline on current good radiopharmacy practice(cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacyand Chemistry (2021)6:8. Clinical and Translational Imaging, 6(8), 281–282. Advance online publication.https://doi.org/10.1007/s40336-021-00437-wCopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 01-11-2023Vol.:(0123456789) Clinical and Translational Imaging https://doi.org/10.1007/s40336-021-00437-wSPOTLIGHTSpotlight on: guideline on current good radiopharmacy practice (cGRPP) for the small‑scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8Nicholas M. Gillings1 · Philip H. Elsinga2Received: 19 April 2021 / Accepted: 21 May 2021 © Italian Association of Nuclear Medicine and Molecular Imaging 2021Radiopharmaceuticals play a central role in nuclear medi-cine imaging. Their binding properties and pharmacokinet-ics are a major determinant of the obtained PET or SPECT image.Since radiopharmaceuticals are considered as medicines, their preparation is subject to the same legislation as for other drugs. One of the requirements is the application of Good Manufacturing Practice (GMP) which in the European Union is described in Eudralex Volume 4—Good Manufac-turing Practice Guidelines.Radiopharmaceuticals are either produced by industry or in hospitals. Industrially produced radiopharmaceuticals are often on a relatively large scale and are shipped to hospitals according to demand. Therefore, in this case, companies apply full GMP as they have sufficient resources to comply with GMP guidelines.In hospitals, radiopharmaceuticals are often prepared on a much smaller scale and are used locally for only a few patients. Usually, these radiopharmaceuticals contain short-lived radionuclides locally produced using a cyclotron or eluted from a generator. Moreover, the commercial interest for such tracers is often limited and they are therefore not commercially available. The combination of the specific characteristics of locally small-scale prepared radiophar-maceuticals with the fact that in hospitals resources is much less compared to industry makes full compliance with regu-lar GMP guidelines very challenging.Therefore, the EANM Radiopharmacy committee has developed a set of guidelines for the small-scale prepara-tion of radiopharmaceuticals according to current good radi-opharmacy practice (cGRPP). With this set of guidelines, EANM offers hospital radiopharmacies guidance on how to ensure high-quality standards appropriate to the specific conditions for the small-scale preparation of radiopharma-ceuticals (SSRP).The recently published guideline is an update of the previously published guidance [2] and also refers to other documents that have since been published by the EANM: Guidance on cGRPP for SSRPs using automated modules: a European perspective [1], Guidelines on the labeling of leucocytes with 99mTc-HMPAO [8], EANM guideline on the validation of analytical methods for radiopharmaceuticals [4], and Guidance on validation and qualification of pro-cesses and operations involving radiopharmaceuticals [7]. Furthermore, this guideline refers to the current legislative documents issues by the European Union [3], Pharmaceuti-cal Inspection Co-operation Scheme (PICs) [6], and IAEA [5].The guideline provides a useful point of reference for hospital radiopharmacies, bringing together several docu-ments published during the last 10 years to aid in the in establishment of quality standards for production of their radiopharmaceuticals. The guideline is in three parts: Part 1 contains general guidance with respect to quality assur-ance, personnel, premises, equipment, documentation, production, quality control and outsourced activities which applies for all diagnostic and therapeutic radiopharmaceu-ticlas. Part 2 contains guidance on the preparation of radi-opharmaceuticals from licensed components (generators, radionuclide precursors and kits). Part 3 contains detailed guidance on the preparation of radiopharmaceuticals from non-licensed components, including the production of  * Philip H. Elsinga  p.h.elsinga@umcg.nl Nicholas M. Gillings  nicholas.mathew.gillings@regionh.dk1 PET & Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark2 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, The Netherlands Clinical and Translational Imaging1 3PET-radiopharmaceuticals from cyclotron-produced radi-onuclides using synthesis modules and other specialized equipment.The following topics are addressed:In part 1, the use of a risk-management approach in the quality assurance (QA) system is emphasized. Fur-thermore, the requirement of having a responsible person for radiopharmaceuticals (RPR) is promoted, whereas in the general EU GMP guidelines, a qualified person (QP) is mentioned. It must be highlighted here that the require-ment for certification of radiopharmaceuticals by a QP is dependent on the type of product and applicable national legislation. Furthermore, the importance of having systems for handling deviations, changes, out of specification results (OOS) and corrective and preventative actions (CAPA) is stressed. Regarding personnel, it is described that sufficient staff must be available who have appropriate education and training. This can be offered by EANM/ESMIT at different levels, from e-learning to postgraduate courses and advanced courses. It is also stressed that, for outsourced activities, such as cleaning, monitoring, tests and qualification, written contracts should be in place.Overall, in part 1, it is described how a high level of quality assurance can be maintained in a small hospital radiopharmacy.In part 2, which covers preparation from licensed compo-nents, the following topics are explicitly described: premises and equipment, production, and quality control.For production of SSRPs from non-licensed components, as described in Part 3, a dedicated quality management system is recommended. Furthermore, besides the RPR, a separate production manager and quality control manager should ideally be available. For these radiopharmaceuticals, automated synthesis systems are often used. Conditions for the use of such systems along with validation of production processes are described. Specifically mentioned are biobur-den tests and identification of critical steps that can affect microbiology. Vendor qualification is discussed and it is rec-ommended to perform supplier audits. EANM has taken the initiative to organize joint audits under the SASAI initiative.In conclusion, the newly published guideline offers a comprehensive and up-to-date overview with reference to other applicable publications, and gives practical advice for hospital radiopharmacies with respect to the small-scale preparation of radiopharmaceuticals.Funding No funding was obtained.Declarations Conflict of interest The authors declare no competing financial inter-ests. Nic Gillings is first author of the spotlighted article and is member of the EANM Radiopharmacy Committee. Philip Elsinga is co-author of the spotlighted article and Editor-in-Chief of European Journal of Nuclear Medicine and Molecular Imaging Radiopharmacy and Chem-istry.Consent for publication All authors gave their consent for publication.References 1. Aerts J, Ballinger JR, Behe M, Decristoforo C, Elsinga PH, Faivre-Chauvet A, Mindt TL, KolencPeitl P, Todde S, Koziorowski J (2014) Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Labelled Compd Radiopharm 57:615–620 2. Elsinga P, Todde S, Penuelas I, Meyer G, Farstad B, Faivre-Chau-vet A, Mikolajczak R, Westera G, Gmeiner-Stopar T, Decristo-foro C (2010) Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 37(5):1049–1062 3. EU GMP, Volume 4 Good manufacturing practice (GMP) Guide-lines. https:// ec. europa. eu/ health/ docum ents/ eudra lex/ vol-4_ en. Accessed 30 Apr 2020 4. Gillings N, Todde S, Behe M, Decristoforo C, Elsinga P, Ferrari V, Hjelstuen O, KolencPeitl P, Koziorowski J, Laverman P, Mindt TL, Ocak M, Patt M (2020) EANM guideline on the validation of analytical methods for radiopharmaceuticals EJNMMI radiophar-macy and chemistry. EJNMMI Radiopharm Chem 5:7 5. IAEA Operational Guidance on Hospital Radiopharmacy (2008) https:// www. iaea. org/ publi catio ns/ 7708/ opera tional- guida nce- on- hospi tal- radio pharm acy 6. PIC/S Guide to good practices for the preparation of medicinal products in healthcare establishments. Version PE 010–4, March 2014. https:// www. picsc heme. org/ en/ publi catio ns. Accessed 30 Apr 2020 7. Todde S, KolencPeitl P, Elsinga P, Koziorowski J, Ferrari V, Ocak EM, Hjelstuen O, Patt M, Mindt TL, Behe M (2017) Guidance on validation and qualification of processes and operations involving radiopharmaceuticals. EJNMMI Radiopharm Chem 2:8 8. de Vries EJF, Roca M, Jamar F, Israel O, Signore A (2010) Guide-lines for the labelling of leucocytes with 99mTc-HMPAO. Eur J Nucl Med Mol Imaging 37:842–848Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Dissertations of the University of Groningen

   University of GroningenSpotlight onGillings, Nicholas M.; Elsinga, Philip H.Published in:Clinical and Translational ImagingDOI:10.1007/s40336-021-00437-wIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2021Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Gillings, N. M., & Elsinga, P. H. (2021). Spotlight on: guideline on current good radiopharmacy practice(cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacyand Chemistry (2021)6:8. Clinical and Translational Imaging, 6(8), 281–282.https://doi.org/10.1007/s40336-021-00437-wCopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 01-02-2024Vol.:(0123456789) Clinical and Translational Imaging https://doi.org/10.1007/s40336-021-00437-wSPOTLIGHTSpotlight on: guideline on current good radiopharmacy practice (cGRPP) for the small‑scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8Nicholas M. Gillings1 · Philip H. Elsinga2Received: 19 April 2021 / Accepted: 21 May 2021 © Italian Association of Nuclear Medicine and Molecular Imaging 2021Radiopharmaceuticals play a central role in nuclear medi-cine imaging. Their binding properties and pharmacokinet-ics are a major determinant of the obtained PET or SPECT image.Since radiopharmaceuticals are considered as medicines, their preparation is subject to the same legislation as for other drugs. One of the requirements is the application of Good Manufacturing Practice (GMP) which in the European Union is described in Eudralex Volume 4—Good Manufac-turing Practice Guidelines.Radiopharmaceuticals are either produced by industry or in hospitals. Industrially produced radiopharmaceuticals are often on a relatively large scale and are shipped to hospitals according to demand. Therefore, in this case, companies apply full GMP as they have sufficient resources to comply with GMP guidelines.In hospitals, radiopharmaceuticals are often prepared on a much smaller scale and are used locally for only a few patients. Usually, these radiopharmaceuticals contain short-lived radionuclides locally produced using a cyclotron or eluted from a generator. Moreover, the commercial interest for such tracers is often limited and they are therefore not commercially available. The combination of the specific characteristics of locally small-scale prepared radiophar-maceuticals with the fact that in hospitals resources is much less compared to industry makes full compliance with regu-lar GMP guidelines very challenging.Therefore, the EANM Radiopharmacy committee has developed a set of guidelines for the small-scale prepara-tion of radiopharmaceuticals according to current good radi-opharmacy practice (cGRPP). With this set of guidelines, EANM offers hospital radiopharmacies guidance on how to ensure high-quality standards appropriate to the specific conditions for the small-scale preparation of radiopharma-ceuticals (SSRP).The recently published guideline is an update of the previously published guidance [2] and also refers to other documents that have since been published by the EANM: Guidance on cGRPP for SSRPs using automated modules: a European perspective [1], Guidelines on the labeling of leucocytes with 99mTc-HMPAO [8], EANM guideline on the validation of analytical methods for radiopharmaceuticals [4], and Guidance on validation and qualification of pro-cesses and operations involving radiopharmaceuticals [7]. Furthermore, this guideline refers to the current legislative documents issues by the European Union [3], Pharmaceuti-cal Inspection Co-operation Scheme (PICs) [6], and IAEA [5].The guideline provides a useful point of reference for hospital radiopharmacies, bringing together several docu-ments published during the last 10 years to aid in the in establishment of quality standards for production of their radiopharmaceuticals. The guideline is in three parts: Part 1 contains general guidance with respect to quality assur-ance, personnel, premises, equipment, documentation, production, quality control and outsourced activities which applies for all diagnostic and therapeutic radiopharmaceu-ticlas. Part 2 contains guidance on the preparation of radi-opharmaceuticals from licensed components (generators, radionuclide precursors and kits). Part 3 contains detailed guidance on the preparation of radiopharmaceuticals from non-licensed components, including the production of  * Philip H. Elsinga  p.h.elsinga@umcg.nl Nicholas M. Gillings  nicholas.mathew.gillings@regionh.dk1 PET & Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark2 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, The Netherlands Clinical and Translational Imaging1 3PET-radiopharmaceuticals from cyclotron-produced radi-onuclides using synthesis modules and other specialized equipment.The following topics are addressed:In part 1, the use of a risk-management approach in the quality assurance (QA) system is emphasized. Fur-thermore, the requirement of having a responsible person for radiopharmaceuticals (RPR) is promoted, whereas in the general EU GMP guidelines, a qualified person (QP) is mentioned. It must be highlighted here that the require-ment for certification of radiopharmaceuticals by a QP is dependent on the type of product and applicable national legislation. Furthermore, the importance of having systems for handling deviations, changes, out of specification results (OOS) and corrective and preventative actions (CAPA) is stressed. Regarding personnel, it is described that sufficient staff must be available who have appropriate education and training. This can be offered by EANM/ESMIT at different levels, from e-learning to postgraduate courses and advanced courses. It is also stressed that, for outsourced activities, such as cleaning, monitoring, tests and qualification, written contracts should be in place.Overall, in part 1, it is described how a high level of quality assurance can be maintained in a small hospital radiopharmacy.In part 2, which covers preparation from licensed compo-nents, the following topics are explicitly described: premises and equipment, production, and quality control.For production of SSRPs from non-licensed components, as described in Part 3, a dedicated quality management system is recommended. Furthermore, besides the RPR, a separate production manager and quality control manager should ideally be available. For these radiopharmaceuticals, automated synthesis systems are often used. Conditions for the use of such systems along with validation of production processes are described. Specifically mentioned are biobur-den tests and identification of critical steps that can affect microbiology. Vendor qualification is discussed and it is rec-ommended to perform supplier audits. EANM has taken the initiative to organize joint audits under the SASAI initiative.In conclusion, the newly published guideline offers a comprehensive and up-to-date overview with reference to other applicable publications, and gives practical advice for hospital radiopharmacies with respect to the small-scale preparation of radiopharmaceuticals.Funding No funding was obtained.Declarations Conflict of interest The authors declare no competing financial inter-ests. Nic Gillings is first author of the spotlighted article and is member of the EANM Radiopharmacy Committee. Philip Elsinga is co-author of the spotlighted article and Editor-in-Chief of European Journal of Nuclear Medicine and Molecular Imaging Radiopharmacy and Chem-istry.Consent for publication All authors gave their consent for publication.References 1. Aerts J, Ballinger JR, Behe M, Decristoforo C, Elsinga PH, Faivre-Chauvet A, Mindt TL, KolencPeitl P, Todde S, Koziorowski J (2014) Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Labelled Compd Radiopharm 57:615–620 2. Elsinga P, Todde S, Penuelas I, Meyer G, Farstad B, Faivre-Chau-vet A, Mikolajczak R, Westera G, Gmeiner-Stopar T, Decristo-foro C (2010) Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 37(5):1049–1062 3. EU GMP, Volume 4 Good manufacturing practice (GMP) Guide-lines. https:// ec. europa. eu/ health/ docum ents/ eudra lex/ vol-4_ en. Accessed 30 Apr 2020 4. Gillings N, Todde S, Behe M, Decristoforo C, Elsinga P, Ferrari V, Hjelstuen O, KolencPeitl P, Koziorowski J, Laverman P, Mindt TL, Ocak M, Patt M (2020) EANM guideline on the validation of analytical methods for radiopharmaceuticals EJNMMI radiophar-macy and chemistry. EJNMMI Radiopharm Chem 5:7 5. IAEA Operational Guidance on Hospital Radiopharmacy (2008) https:// www. iaea. org/ publi catio ns/ 7708/ opera tional- guida nce- on- hospi tal- radio pharm acy 6. PIC/S Guide to good practices for the preparation of medicinal products in healthcare establishments. Version PE 010–4, March 2014. https:// www. picsc heme. org/ en/ publi catio ns. Accessed 30 Apr 2020 7. Todde S, KolencPeitl P, Elsinga P, Koziorowski J, Ferrari V, Ocak EM, Hjelstuen O, Patt M, Mindt TL, Behe M (2017) Guidance on validation and qualification of processes and operations involving radiopharmaceuticals. EJNMMI Radiopharm Chem 2:8 8. de Vries EJF, Roca M, Jamar F, Israel O, Signore A (2010) Guide-lines for the labelling of leucocytes with 99mTc-HMPAO. Eur J Nucl Med Mol Imaging 37:842–848Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

   University of GroningenSpotlight onGillings, Nicholas M.; Elsinga, Philip H.Published in:Clinical and Translational ImagingDOI:10.1007/s40336-021-00437-wIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2021Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Gillings, N. M., & Elsinga, P. H. (2021). Spotlight on: guideline on current good radiopharmacy practice(cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacyand Chemistry (2021)6:8. Clinical and Translational Imaging, 6(8), 281–282.https://doi.org/10.1007/s40336-021-00437-wCopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-10-2022Vol.:(0123456789) Clinical and Translational Imaging https://doi.org/10.1007/s40336-021-00437-wSPOTLIGHTSpotlight on: guideline on current good radiopharmacy practice (cGRPP) for the small‑scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8Nicholas M. Gillings1 · Philip H. Elsinga2Received: 19 April 2021 / Accepted: 21 May 2021 © Italian Association of Nuclear Medicine and Molecular Imaging 2021Radiopharmaceuticals play a central role in nuclear medi-cine imaging. Their binding properties and pharmacokinet-ics are a major determinant of the obtained PET or SPECT image.Since radiopharmaceuticals are considered as medicines, their preparation is subject to the same legislation as for other drugs. One of the requirements is the application of Good Manufacturing Practice (GMP) which in the European Union is described in Eudralex Volume 4—Good Manufac-turing Practice Guidelines.Radiopharmaceuticals are either produced by industry or in hospitals. Industrially produced radiopharmaceuticals are often on a relatively large scale and are shipped to hospitals according to demand. Therefore, in this case, companies apply full GMP as they have sufficient resources to comply with GMP guidelines.In hospitals, radiopharmaceuticals are often prepared on a much smaller scale and are used locally for only a few patients. Usually, these radiopharmaceuticals contain short-lived radionuclides locally produced using a cyclotron or eluted from a generator. Moreover, the commercial interest for such tracers is often limited and they are therefore not commercially available. The combination of the specific characteristics of locally small-scale prepared radiophar-maceuticals with the fact that in hospitals resources is much less compared to industry makes full compliance with regu-lar GMP guidelines very challenging.Therefore, the EANM Radiopharmacy committee has developed a set of guidelines for the small-scale prepara-tion of radiopharmaceuticals according to current good radi-opharmacy practice (cGRPP). With this set of guidelines, EANM offers hospital radiopharmacies guidance on how to ensure high-quality standards appropriate to the specific conditions for the small-scale preparation of radiopharma-ceuticals (SSRP).The recently published guideline is an update of the previously published guidance [2] and also refers to other documents that have since been published by the EANM: Guidance on cGRPP for SSRPs using automated modules: a European perspective [1], Guidelines on the labeling of leucocytes with 99mTc-HMPAO [8], EANM guideline on the validation of analytical methods for radiopharmaceuticals [4], and Guidance on validation and qualification of pro-cesses and operations involving radiopharmaceuticals [7]. Furthermore, this guideline refers to the current legislative documents issues by the European Union [3], Pharmaceuti-cal Inspection Co-operation Scheme (PICs) [6], and IAEA [5].The guideline provides a useful point of reference for hospital radiopharmacies, bringing together several docu-ments published during the last 10 years to aid in the in establishment of quality standards for production of their radiopharmaceuticals. The guideline is in three parts: Part 1 contains general guidance with respect to quality assur-ance, personnel, premises, equipment, documentation, production, quality control and outsourced activities which applies for all diagnostic and therapeutic radiopharmaceu-ticlas. Part 2 contains guidance on the preparation of radi-opharmaceuticals from licensed components (generators, radionuclide precursors and kits). Part 3 contains detailed guidance on the preparation of radiopharmaceuticals from non-licensed components, including the production of  * Philip H. Elsinga  p.h.elsinga@umcg.nl Nicholas M. Gillings  nicholas.mathew.gillings@regionh.dk1 PET & Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark2 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, The Netherlands Clinical and Translational Imaging1 3PET-radiopharmaceuticals from cyclotron-produced radi-onuclides using synthesis modules and other specialized equipment.The following topics are addressed:In part 1, the use of a risk-management approach in the quality assurance (QA) system is emphasized. Fur-thermore, the requirement of having a responsible person for radiopharmaceuticals (RPR) is promoted, whereas in the general EU GMP guidelines, a qualified person (QP) is mentioned. It must be highlighted here that the require-ment for certification of radiopharmaceuticals by a QP is dependent on the type of product and applicable national legislation. Furthermore, the importance of having systems for handling deviations, changes, out of specification results (OOS) and corrective and preventative actions (CAPA) is stressed. Regarding personnel, it is described that sufficient staff must be available who have appropriate education and training. This can be offered by EANM/ESMIT at different levels, from e-learning to postgraduate courses and advanced courses. It is also stressed that, for outsourced activities, such as cleaning, monitoring, tests and qualification, written contracts should be in place.Overall, in part 1, it is described how a high level of quality assurance can be maintained in a small hospital radiopharmacy.In part 2, which covers preparation from licensed compo-nents, the following topics are explicitly described: premises and equipment, production, and quality control.For production of SSRPs from non-licensed components, as described in Part 3, a dedicated quality management system is recommended. Furthermore, besides the RPR, a separate production manager and quality control manager should ideally be available. For these radiopharmaceuticals, automated synthesis systems are often used. Conditions for the use of such systems along with validation of production processes are described. Specifically mentioned are biobur-den tests and identification of critical steps that can affect microbiology. Vendor qualification is discussed and it is rec-ommended to perform supplier audits. EANM has taken the initiative to organize joint audits under the SASAI initiative.In conclusion, the newly published guideline offers a comprehensive and up-to-date overview with reference to other applicable publications, and gives practical advice for hospital radiopharmacies with respect to the small-scale preparation of radiopharmaceuticals.Funding No funding was obtained.Declarations Conflict of interest The authors declare no competing financial inter-ests. Nic Gillings is first author of the spotlighted article and is member of the EANM Radiopharmacy Committee. Philip Elsinga is co-author of the spotlighted article and Editor-in-Chief of European Journal of Nuclear Medicine and Molecular Imaging Radiopharmacy and Chem-istry.Consent for publication All authors gave their consent for publication.References 1. Aerts J, Ballinger JR, Behe M, Decristoforo C, Elsinga PH, Faivre-Chauvet A, Mindt TL, KolencPeitl P, Todde S, Koziorowski J (2014) Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Labelled Compd Radiopharm 57:615–620 2. Elsinga P, Todde S, Penuelas I, Meyer G, Farstad B, Faivre-Chau-vet A, Mikolajczak R, Westera G, Gmeiner-Stopar T, Decristo-foro C (2010) Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 37(5):1049–1062 3. EU GMP, Volume 4 Good manufacturing practice (GMP) Guide-lines. https:// ec. europa. eu/ health/ docum ents/ eudra lex/ vol-4_ en. Accessed 30 Apr 2020 4. Gillings N, Todde S, Behe M, Decristoforo C, Elsinga P, Ferrari V, Hjelstuen O, KolencPeitl P, Koziorowski J, Laverman P, Mindt TL, Ocak M, Patt M (2020) EANM guideline on the validation of analytical methods for radiopharmaceuticals EJNMMI radiophar-macy and chemistry. EJNMMI Radiopharm Chem 5:7 5. IAEA Operational Guidance on Hospital Radiopharmacy (2008) https:// www. iaea. org/ publi catio ns/ 7708/ opera tional- guida nce- on- hospi tal- radio pharm acy 6. PIC/S Guide to good practices for the preparation of medicinal products in healthcare establishments. Version PE 010–4, March 2014. https:// www. picsc heme. org/ en/ publi catio ns. Accessed 30 Apr 2020 7. Todde S, KolencPeitl P, Elsinga P, Koziorowski J, Ferrari V, Ocak EM, Hjelstuen O, Patt M, Mindt TL, Behe M (2017) Guidance on validation and qualification of processes and operations involving radiopharmaceuticals. EJNMMI Radiopharm Chem 2:8 8. de Vries EJF, Roca M, Jamar F, Israel O, Signore A (2010) Guide-lines for the labelling of leucocytes with 99mTc-HMPAO. Eur J Nucl Med Mol Imaging 37:842–848Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

   University of GroningenSpotlight onGillings, Nicholas M.; Elsinga, Philip H.Published in:Clinical and Translational ImagingDOI:10.1007/s40336-021-00437-wIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2021Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Gillings, N. M., & Elsinga, P. H. (2021). Spotlight on: guideline on current good radiopharmacy practice(cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacyand Chemistry (2021)6:8. Clinical and Translational Imaging, 6(8), 281–282.https://doi.org/10.1007/s40336-021-00437-wCopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 29-04-2023Vol.:(0123456789) Clinical and Translational Imaging https://doi.org/10.1007/s40336-021-00437-wSPOTLIGHTSpotlight on: guideline on current good radiopharmacy practice (cGRPP) for the small‑scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8Nicholas M. Gillings1 · Philip H. Elsinga2Received: 19 April 2021 / Accepted: 21 May 2021 © Italian Association of Nuclear Medicine and Molecular Imaging 2021Radiopharmaceuticals play a central role in nuclear medi-cine imaging. Their binding properties and pharmacokinet-ics are a major determinant of the obtained PET or SPECT image.Since radiopharmaceuticals are considered as medicines, their preparation is subject to the same legislation as for other drugs. One of the requirements is the application of Good Manufacturing Practice (GMP) which in the European Union is described in Eudralex Volume 4—Good Manufac-turing Practice Guidelines.Radiopharmaceuticals are either produced by industry or in hospitals. Industrially produced radiopharmaceuticals are often on a relatively large scale and are shipped to hospitals according to demand. Therefore, in this case, companies apply full GMP as they have sufficient resources to comply with GMP guidelines.In hospitals, radiopharmaceuticals are often prepared on a much smaller scale and are used locally for only a few patients. Usually, these radiopharmaceuticals contain short-lived radionuclides locally produced using a cyclotron or eluted from a generator. Moreover, the commercial interest for such tracers is often limited and they are therefore not commercially available. The combination of the specific characteristics of locally small-scale prepared radiophar-maceuticals with the fact that in hospitals resources is much less compared to industry makes full compliance with regu-lar GMP guidelines very challenging.Therefore, the EANM Radiopharmacy committee has developed a set of guidelines for the small-scale prepara-tion of radiopharmaceuticals according to current good radi-opharmacy practice (cGRPP). With this set of guidelines, EANM offers hospital radiopharmacies guidance on how to ensure high-quality standards appropriate to the specific conditions for the small-scale preparation of radiopharma-ceuticals (SSRP).The recently published guideline is an update of the previously published guidance [2] and also refers to other documents that have since been published by the EANM: Guidance on cGRPP for SSRPs using automated modules: a European perspective [1], Guidelines on the labeling of leucocytes with 99mTc-HMPAO [8], EANM guideline on the validation of analytical methods for radiopharmaceuticals [4], and Guidance on validation and qualification of pro-cesses and operations involving radiopharmaceuticals [7]. Furthermore, this guideline refers to the current legislative documents issues by the European Union [3], Pharmaceuti-cal Inspection Co-operation Scheme (PICs) [6], and IAEA [5].The guideline provides a useful point of reference for hospital radiopharmacies, bringing together several docu-ments published during the last 10 years to aid in the in establishment of quality standards for production of their radiopharmaceuticals. The guideline is in three parts: Part 1 contains general guidance with respect to quality assur-ance, personnel, premises, equipment, documentation, production, quality control and outsourced activities which applies for all diagnostic and therapeutic radiopharmaceu-ticlas. Part 2 contains guidance on the preparation of radi-opharmaceuticals from licensed components (generators, radionuclide precursors and kits). Part 3 contains detailed guidance on the preparation of radiopharmaceuticals from non-licensed components, including the production of  * Philip H. Elsinga  p.h.elsinga@umcg.nl Nicholas M. Gillings  nicholas.mathew.gillings@regionh.dk1 PET & Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Denmark2 Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713GZ Groningen, The Netherlands Clinical and Translational Imaging1 3PET-radiopharmaceuticals from cyclotron-produced radi-onuclides using synthesis modules and other specialized equipment.The following topics are addressed:In part 1, the use of a risk-management approach in the quality assurance (QA) system is emphasized. Fur-thermore, the requirement of having a responsible person for radiopharmaceuticals (RPR) is promoted, whereas in the general EU GMP guidelines, a qualified person (QP) is mentioned. It must be highlighted here that the require-ment for certification of radiopharmaceuticals by a QP is dependent on the type of product and applicable national legislation. Furthermore, the importance of having systems for handling deviations, changes, out of specification results (OOS) and corrective and preventative actions (CAPA) is stressed. Regarding personnel, it is described that sufficient staff must be available who have appropriate education and training. This can be offered by EANM/ESMIT at different levels, from e-learning to postgraduate courses and advanced courses. It is also stressed that, for outsourced activities, such as cleaning, monitoring, tests and qualification, written contracts should be in place.Overall, in part 1, it is described how a high level of quality assurance can be maintained in a small hospital radiopharmacy.In part 2, which covers preparation from licensed compo-nents, the following topics are explicitly described: premises and equipment, production, and quality control.For production of SSRPs from non-licensed components, as described in Part 3, a dedicated quality management system is recommended. Furthermore, besides the RPR, a separate production manager and quality control manager should ideally be available. For these radiopharmaceuticals, automated synthesis systems are often used. Conditions for the use of such systems along with validation of production processes are described. Specifically mentioned are biobur-den tests and identification of critical steps that can affect microbiology. Vendor qualification is discussed and it is rec-ommended to perform supplier audits. EANM has taken the initiative to organize joint audits under the SASAI initiative.In conclusion, the newly published guideline offers a comprehensive and up-to-date overview with reference to other applicable publications, and gives practical advice for hospital radiopharmacies with respect to the small-scale preparation of radiopharmaceuticals.Funding No funding was obtained.Declarations Conflict of interest The authors declare no competing financial inter-ests. Nic Gillings is first author of the spotlighted article and is member of the EANM Radiopharmacy Committee. Philip Elsinga is co-author of the spotlighted article and Editor-in-Chief of European Journal of Nuclear Medicine and Molecular Imaging Radiopharmacy and Chem-istry.Consent for publication All authors gave their consent for publication.References 1. Aerts J, Ballinger JR, Behe M, Decristoforo C, Elsinga PH, Faivre-Chauvet A, Mindt TL, KolencPeitl P, Todde S, Koziorowski J (2014) Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Labelled Compd Radiopharm 57:615–620 2. Elsinga P, Todde S, Penuelas I, Meyer G, Farstad B, Faivre-Chau-vet A, Mikolajczak R, Westera G, Gmeiner-Stopar T, Decristo-foro C (2010) Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 37(5):1049–1062 3. EU GMP, Volume 4 Good manufacturing practice (GMP) Guide-lines. https:// ec. europa. eu/ health/ docum ents/ eudra lex/ vol-4_ en. Accessed 30 Apr 2020 4. Gillings N, Todde S, Behe M, Decristoforo C, Elsinga P, Ferrari V, Hjelstuen O, KolencPeitl P, Koziorowski J, Laverman P, Mindt TL, Ocak M, Patt M (2020) EANM guideline on the validation of analytical methods for radiopharmaceuticals EJNMMI radiophar-macy and chemistry. EJNMMI Radiopharm Chem 5:7 5. IAEA Operational Guidance on Hospital Radiopharmacy (2008) https:// www. iaea. org/ publi catio ns/ 7708/ opera tional- guida nce- on- hospi tal- radio pharm acy 6. PIC/S Guide to good practices for the preparation of medicinal products in healthcare establishments. Version PE 010–4, March 2014. https:// www. picsc heme. org/ en/ publi catio ns. Accessed 30 Apr 2020 7. Todde S, KolencPeitl P, Elsinga P, Koziorowski J, Ferrari V, Ocak EM, Hjelstuen O, Patt M, Mindt TL, Behe M (2017) Guidance on validation and qualification of processes and operations involving radiopharmaceuticals. EJNMMI Radiopharm Chem 2:8 8. de Vries EJF, Roca M, Jamar F, Israel O, Signore A (2010) Guide-lines for the labelling of leucocytes with 99mTc-HMPAO. Eur J Nucl Med Mol Imaging 37:842–848Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Spotlight on:guideline on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals published in EJNMMI Radiopharmacy and Chemistry (2021)6:8

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