Guidance on current good radiopharmacy practice for the small‐scale preparation of radiopharmaceuticals using automated modules: a European perspective

Abstract

This document is meant to complement Part B of the EANM 'Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals' issued by the Radiopharmacy Committee of the European Association of Nuclear Medicine, covering small-scale in-house preparation of radiopharmaceuticals with automated modules. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of radiopharmaceuticals, which are not intended for commercial purposes or distribution.Keywords: radiopharmaceutical; positron emission tomography; single-photon emission computed tomography; process validation; automated radiosynthesis module Definitions (see also references 1 and 2) Radiopharmaceutical A radiopharmaceutical is any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. Small-scale radiopharmaceuticalA small-scale radiopharmaceutical is any in-house radiopharmaceutical not intended for commercial purposes or distribution, prepared on a small scale, excluding preparations based on licensed generators and labelling kits, and excluding preparation of kits. Finished productA finished product is a medicinal product that has undergone all stages of production, including packaging in its final container and labelling. PreparationPreparation includes all operations involved in the purchase of materials and products, production, QC, release and storage of a medicinal product and the related controls. Small-scale radiopharmacyA small-scale radiopharmacy is a facility where small-scale preparation of radiopharmaceuticals is carried out in accordance with national regulations for in-house use. The term small-scale radiopharmacy is not related to the physical size of the facility.

Pitfalls and Limitations of SPECT, PET, and Therapeutic Radiopharmaceuticals

“…This may be somewhat surprising in light of the great advances in automation of PET radiopharmaceutical preparation. 19 The switch from highly enriched 235 U to low enrichment 235 U in the production of 99 Mo for generators has no significance for the chemical properties of the 99m Tc pertechnetate eluate. 20 However, if use of cyclotron-produced 99m Tc becomes a reality, there are a number of implications for kit preparation.…”

The main issues of quality assurance of radiopharmaceuticals

“…Возникла некоторая аналогия ситуации, существующей в США или ЕС. Например, в соответствии со статьей 7 Директивы 2001/83 EC 27 : «Торговая лицензия не требуется для радиофармацевтического лекарственного средства, приготовленного во время применения лицом или учреждением, уполномоченным, в соответствии с национальным законодательством, применять такие лекарственные средства в лицензирован-ных учреждениях здравоохранения исключительно из лицензированных генераторов радионуклидов, наборов или прекурсоров радионуклидов в соответствии с инструкциями производителя». Однако соответствующий подзаконный акт 28 был принят только через 5 лет после вступления в силу Федерального закона № 61-ФЗ.…”

“…Draft EMA/CHMP/SWP/686140/2018. 27 Директива 2001/83/ЕС Европейского парламента и Совета ЕС от 6 ноября 2001 г. «О своде законов Сообщества в отношении лекарственных средств для человека с изменениями».…”

“…В 2010 г. часть В была существенно дополнена с учетом публикации FDA 31 и опубликована в журнале EANM отдельной статьей [26]. Позже, в 2014 г., появилось «Руководство по надлежащей практике изготовления радиофармпрепаратов с использованием модулей синтеза» [27], а в 2017 г. -«Руководство по валидации и квалификации процессов и операций, связанных с радиофармацевтическими препаратами» [28].…”

Have you looked for “stranger things” in your automated PET dose dispensing system? A process and operators qualification scheme

“…Inspired by guidance for qualification of small-scale PET radiopharmaceutical synthesis modules, and in respect with the Pharmaceutical Inspection Co-operation Scheme (PIC/S), the European Pharmacopeia and the Food and Drug Administration (FDA) guidance, we set up a master plan validation in a radiopharmacy equipped with Trasis Unidose®, including: 1) monthly specific process-simulating media-fill tests (MFT) and microbiological contamination assessments of our ADS surfaces; 2) initial qualification and yearly requalification of the ADS operators (Aerts et al 2014; PIC/S n.d.; Food and Drug Administration CDER CGMP 2012). The first six-month follow-up period already showed the importance of implementing and long-term pursuing such a process to ensure the continuous performances of the ADS and good practices application.…”