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Biopharmaceuticals are associated with the revolutionary treatment of various diseases, and according to the European Medicines Agency, biopharmaceuticals derived from biological sources are perceived to not cause significant environmental risk. However, there is currently no broadly recognized definition or categorization of biopharmaceuticals despite the fact that improved technology has made it possible to modify them to obtain more efficient medicines, thereby raising questions about their biological origins and risks. The aim of this paper, based on a literature review, is to derive a clear definition of biopharmaceuticals and evaluate the European Union's regulation and environmental risk assessment (ERA) procedures for them. Nine different definitions were identified, and it is evident that the term “biopharmaceuticals” is used ambiguously. We therefore recommend that biopharmaceuticals are defined as complex molecules derived from a biological source, with the purpose to diagnose, prevent, treat, or cure diseases or conditions of human beings. Furthermore, we recommend that biopharmaceuticals should be categorized according to their biological structure: 1) amino acids, 2) nucleic acids, and 3) vaccines. Only 11 studies were identified as being relevant to ERA, and we lack useful data for hazard identification. More research is needed to examine the ecotoxicity, fate, and stability of most biopharmaceuticals—and categorical regulatory exclusion seems unfavorable in this regard.

On 18 September 2017, a marketing authorisation valid through the European Union (EU) was issued for midostaurin in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy and for patients in complete response followed by midostaurin single agent maintenance therapy, for adult patients with newly diagnosed acute myeloid leukaemia (AML) who are Fms-like tyrosine kinase 3 mutation positive and as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasm (SM-AHN) or mast cell leukaemia (MCL). The recommended dose of midostaurin is 50 mg orally twice daily for AML and 100 mg orally twice daily for ASM, SM-AHN and MCL. Midostaurin was evaluated in two pivotal studies. Study A2301 (RATIFY) included 717 patients with AML. Overall survival (OS) was statistically significantly different between the two groups, and the median OS was 74.7 months in the midostaurin+daunorubicin+cytarabine group and 25.6 months in the placebo+daunorubicin+cytarabine group (HR 0.774; 95% CI 0.629 to 0.953; p=0.0078). Study D2201 included 116 patients with ASM, SM-AHN or MCL. An overall response rate, by IWG-MRT/ECNM (international working group – myelofibrosis research and treatment/European competence network on mastocytosis) criteria of 28.3% was observed in all patients and 60.0%, 20.8% and 33.3% in patients with ASM, SM-AHN and MCL respectively. The most common adverse drug reactions (ADRs) with midostaurin treatment in AML were febrile neutropenia, nausea, exfoliative dermatitis, vomiting, headache, petechiae and fever. In ASM, SM-AHN, MCL the most common ADRs were nausea, vomiting, diarrhoea, peripheral oedema and fatigue. The objective of this paper is to summarise the scientific review of the application leading to regulatory approval in the EU.