Are we “preparing” radiopharmaceuticals?

© I a l Today drugs are almost exclusively manufactured industrially. This has been driven by cost savings, but also by a public mandate of high quality and especially standardization, that is difficult to maintain in a non-industrial setting. On the other hand the same public asks for “personalized”or “precision medicine”(Reza Mirnezami et al. 2012) precisely tailored to each patient’s requirements. The more personalized medicines becomes, the less effective a large industrial production can be. In such a situation, not only drug manufacturers have to adopt their strategies, but also the regulatory framework, in which medicine is embedded and drugs are produced, has to implement these trends. That also holds true for radiopharmaceuticals (Lange et al. 2015). Stimulated by activities especially of the EANM and its Radiopharmacy Committee, which drafted a number of guidelines and guidance documents (e.g. (Elsinga et al. 2010; Aerts et al. 2014)), recently PIC/S has released specific guidelines for radiopharmaceuticals prepared in healthcare establishments (Pharmaceutical Inspection Co-operation Scheme. Document PE 010–4 and Annex 3: Good practices for the preparation of radiopharmaceuticals in healthcare establishments 2014) and the EDQM has published a chapter on the “Extemporaneous Preparation of Radiopharmaceuticals” (Extemporaneous preparation of radiopharmaceutical preparations. Chapter 5.19). In these documents a clear distinction is made between industrial and small scale extemporaneous preparation of radiopharmaceuticals, providing guidance on “Good Practices” distinct from industrial standards. The European Parliament and the European Commission now recently have issued a legal act that regulates the requirements for clinical trials within the European Union (EU regulation No 536/2014). The overall purpose of this regulation was to facilitate and harmonise clinical research in the member states and therefore the regulation has very clearly exempted the preparation of radiopharmaceuticals from the requirements of GMP (Decristoforo et al. 2014) if it “is carried out in hospitals, health centres or clinics, by pharmacists or other persons legally authorised in the Member State concerned to carry out such process, and if the investigational medicinal products are intended to be used exclusively in hospitals, health centres or clinics taking part in the same clinical trial in the same Member State”, thereby specifying the framework in which it should be applied, not being intended for radiopharmaceuticals manufactured industrially and being distributed. In a similar way a number of European member states have set up a regulatory framework in which radiopharmaceuticals for routine use (i.e. not for clinical trials) can be prepared on site without the requirements of a marketing authorisation. These exemptions can be derived from the definitions in Article 3 of Directive 2001/83 (The European Parliament and the Council of the European Union 2001), the so called magistral and officinal formulae.