All EU authorized biological medicinal products, including biosimilars, have been subject to centralized procedure of marketing authorization granting, as laid down in Regulation (EC) No 726/2004. This means that marketing authorisation application are scientifically evaluated by the European Medicines Agency (EMA) and granted by the European Commission (EC) and the following applies: one application, one evaluation and, for successful applications, one marketing authorisation valid throughout the Europe. An informative guide on biosimilars in the EU for healthcare professionals is available on the EMA website.
Evidence obtained over 15 years of clinical experience show that authorized biosimilar medicinal products are as safe and effective as other biological medicinal products.
The EU has pioneered the regulation of biosimilar medicines by establishing a solid framework for their approval (Directive 2001/83/EC). To date, the EMA has developed a number of regulatory guidelines (overarching , specific and other relevant guidelines). The guidelines have been continuously amended and complemented to keep up with a rapid progress in biotechnology and analytics. The Slovenian Medicinal Products Act (ZZdr-2) implemented the definition and legal basis for marketing authorisation of biosimilar medicinal products, thus providing an appropriate basis for establishing basic rules for the introduction of these medicinal products into the health system.
Committee for Medicinal Products for Human Use (CHMP) and Pharmacovigilance Risk Assessment Committee (PRAC) issued a positive opinion on their quality/efficiency/safety, i.e. a positive opinion on benefit/risk balance. Within its scope of work, CHMP additionally consults with working groups of experts, specialized in the fields of biological medicinal products (Biologics Working Party, BWP) and similar biological medicinal products (Biosimilar Medicines Working Party, BMWP). Assessment of quality/efficiency/safety in European Medicines Agency is being carried out at the highest scientific, technical, and regulatory level, which includes experts from all member states of the European Union. The scientific evaluation of the submitted dossier is prepared by the CHMP on the basis of an assessment of the documentation submitted to ensure the quality, safety and efficacy of the medicinal product. The medicinal product is only authorised once all deficiencies have been corrected and the benefit-risk balance is final. The CHMP’s position is thus reflected in the EMA recommendation, which is the basis for decision to be made by the European Commission to grant the marketing authorization of the product. It should be noted that the marketing authorization gives the holders the right, but not the obligation, to place the medicinal product on the market.
Extrapolation of indications
If a biosimilar is highly similar to a reference medicine and has comparable safety and efficacy in one therapeutic indication, already acquired safety and efficacy data may be extrapolated to other indications already approved for the reference medicine, if scientifically justified. This avoids the repetition of clinical trials that were already conducted by the manufacturer of the reference product. This means that fewer clinical trials or no trials at all need to be carried out with the biosimilar in certain indications. If clinical studies are needed, these are conducted for one relevant indication and, based on all acquired data, extrapolation to the other indications is usually possible.
As biological medicinal products are at a theoretical risk of triggering serious adverse immune reactions, potential immunogenicity should be evaluated for all biological medicinal products, including biosimilars. Nevertheless, experiences show that severe reactions due to an increased immune response to biologicals are very rare or are limited (e.g. in case of transient antidrug antibodies), the nature of immune reactions depends on many factors and therefore, harmful immunogenicity is unlikely after manufacturing changes or after product interchangeability. Immunogenicity is always monitored also after marketing authorization.