title: Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals: a concise overview and practical guidance for a risk-based approach.
abstract: Radiopharmaceuticals are highly regulated, because they are controlled both as regular medicinal products and as radioactive substances. This can pose a hurdle for their development and clinical use. Radiopharmaceuticals are fundamentally different from other medicinal products and these regulations are not always adequate for their production. Strict compliance may have a huge resource impact, without further improving product quality. In this paper we give an overview of the applicable legislation and guidelines and propose a risk-based approach for their implementation. We focus on a few controversial Good Manufacturing Practice topics: cleanroom classification, air pressure regime, cleanroom qualification and microbiological monitoring. We have developed an algorithm to assess the combined risk of microbiological contamination of a radiopharmaceutical preparation process and propose corresponding Good Manufacturing Practice classification levels. In our opinion, the risk of carry-over of radiopharmaceuticals by individuals cannot be contained by pressure differences, and complicated regimes with underpressured rooms are not necessary in most situations. We propose a sterility assurance level of 10 for radiopharmaceuticals that are administered within a working day, irrespective of their use. We suggest the adoption of limits for environmental monitoring of microbial contamination, as proposed by Bruel and colleagues, on behalf of the French Society of Radiopharmacy. Recently launched regulatory documents seem to breathe a more liberal spirit than current legislation and recognize the need for the use of risk assessment. We argue that future legislation be further harmonized and state risk assessment as the gold standard for implementation of drug quality regulations for the preparation of unlicensed radiopharmaceuticals.
authors: aDepartment of Hospital Pharmacy/Radiopharmacy, Meander Medical Centre, Amersfoort bDepartment of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen, Groningen cDepartment of Clinical Pharmacology and Pharmacy dDepartment of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands eDepartment of Nuclear Medicine, University Clinic, Innsbruck, Austria fRadiopharmacy Unit, Department of Nuclear Medicine, University Clinic of Navarra, Pamplona, Spain.
authors: Rogier
authors: R
authors: Lange
authors: Rob
authors: R
authors: ter Heine
authors: Clemens
authors: C
authors: Decristoforo
authors: Iván
authors: I
authors: Peñuelas
authors: Philip H
authors: PH
authors: Elsinga
authors: Monique M L
authors: MM
authors: van der Westerlaken
authors: N Harry
authors: NH
authors: Hendrikse
mesh_terms: D005060:Europe; D006801:Humans; D017410:Practice Guidelines as Topic; D011854:Radiochemistry / Q000331:legislation & jurisprudence / Q000379:methods*; D019275:Radiopharmaceuticals; D018570:Risk Assessment; D012926:Social Control, Formal
chemical_list: D019275:Radiopharmaceuticals