Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals: a concise overview and practical guidance for a risk-based approach

Lange, R., ter Heine, R., Decristoforo, C., Penuelas, I., Elsinga, P. H., van der Westerlaken, M. M. L. & Hendrikse, N. H., May-2015, In : Nuclear Medicine Communications. 36, 5, p. 414-422 9 p.

Research output: Contribution to journalReview articleAcademicpeer-review

  • Rogier Lange
  • Rob ter Heine
  • Clemens Decristoforo
  • Ivan Penuelas
  • Philip H. Elsinga
  • Monique M. L. van der Westerlaken
  • N. Harry Hendrikse

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(-2) 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.

Original languageEnglish
Pages (from-to)414-422
Number of pages9
JournalNuclear Medicine Communications
Issue number5
Publication statusPublished - May-2015


  • Good Manufacturing Practice, guidance, guidelines, legislation, quality assurance, radiopharmaceuticals, risk assessment, CLINICAL-TRIALS, GMP

ID: 20161132