Biological medicinal products
Biological medicinal products contain active substances of biological origin (human, animal, microbiological). Biological medicinal products include immunological medicinal products (i.e. vaccines), medicinal products prepared from human blood or plasma, advanced therapy medicinal products (cell therapy, gene therapy, tissue engineering), medicinal products produced by biotechnology and other medicinal products produced from biological sources. Biological medicines represent an important milestone in the treatment or reduction of symptoms of certain diseases such as cancers, metabolic diseases, musculoskeletal disorders, growth disorders, chronic autoimmune inflammatory rheumatic diseases. These medicines contribute significantly to successful treatment and patient`s quality of life. The development and especially the production of biological medicines is more demanding compared to the chemical active substance products and this is also reflected in the price of these drugs. As original biological medicines lose their market exclusivity, biosimilar medicines (biosimilars), which are the copies of already existing biological medicinal products and are cheaper to develop, can enter the market. Some biosimilar medicines are already present in Slovenian market, however, in near future we expect more and more biosimilars to become available to Slovenian patients.
BIOSIMILARS
A biosimilar medicine is developed to be highly similar to the original biological medicine. The original biological medicine is a medicine that has already been approved and is used in the EU and referred to as the reference medicine. However, the biosimilar is not regarded as a generic of a biological medicine. Generic medicine is usually produced by chemical synthesis it is generally possible to obtain exactly the same molecule. A biosimilar and its reference medicine are essentially the same, though there may be minor differences in their active substances. These minor differences are due to the fact that these active substances are usually large and complex molecules and that they are made by living cells.
Biosimilar medicinal products come from living organisms (e.g. Chinese hamster ovary (CHO) cells, yeast, bacteria) that have been modified using recombinant DNA technology to produce the desired active substance of biological origin (e.g. insulin, growth hormone, monoclonal antibody). Due to the variability of the biological system, the complexity of biological molecules and complex manufacturing processes, there is a certain degree of variability in reference and biosimilar medicinal products. Some degree of variability is inherent to all biological medicines and minor differences may occur among different batches of the same biological medicine. Strict controls are always applied (study of physico-chemical properties, biological activity, impurities, sterility and stability) to ensure that potential differences are within the acceptable limits and that the differences do not affect safety or efficacy.
The biosimilarity with the reference product is established based on comprehensive head-to-head comparison of the biosimilar with the reference medicine to show that there are no clinically significant differences compared to the reference product in terms of quality, biological function, safety, efficacy and immunogenicity. In this context, it should be noted that biosimilars are approved according to the same standards of pharmaceutical quality, safety and efficacy that apply to all biological medicines approved in the EU (e.g. Good Manufacturing Practice, Good Clinical Practice, drug development according to the relevant EMA, ICH and WHO guidelines).
Interchangeability of biologicals and biosimilars
Interchangeability means the possibility of replacing a particular medicinal product with another medicinal product which has the expected same clinical effect. The replacement can be done by switching when the prescriber decides to exchange one medicine for another medicine with the same therapeutic intent, or with a substitution under special conditions when one medicine is dispensed instead of another equivalent medicine at the pharmacy level without consulting the prescriber.
The data from real world experience and from switching studies accumulated by now show that changing reference biological medicinal product to its biosimilar, biosimilar to another biosimilar of the same reference product and biosimilar to its reference product is safe. Therefore, the European Medicines Agency (EMA) recognizes that from the scientific point of view the biosimilars are interchangeable (“Biosimilar medicines can be interchanged”). The decision, however, on whether to allow interchangeable use and substitution at the pharmacy level of the reference biological medicine and the biosimilar falls under the responsibility of EU Member States, which have the necessary legal framework in place and issue regulations, guidelines, and advice in their areas of competence.
JAZMP does not include biologicals and biosimilars on the list of interchangeable medicinal products, as it classifies certain generic medicinal products (Rules defining interchangeable medicines). In Slovenia, as in several other European countries, biological medicines are not allowed to be substituted at the pharmacy level without consulting a doctor. Nevertheless, at the beginning of the treatment, the doctor has an option to choose a biosimilar.
The JAZMP’s position is that a physician-led switching between authorized versions of a given biologic medicine at treatment initiation or during ongoing treatment is safe. Switching can apply to the following situations:
- switching from reference medicine to biosimilar medicine
- switching from biosimilar medicine to reference medicine
- switching from a biosimilar medicine to another biosimilar medicine, based on the same reference product.
The decision to prescribe a biological medicine for an individual patient, whether it is a reference product or a biosimilar, is limited to performed in the clinical environment and is subject to the clinician’s medical consultation with the patient. As with all biologic medicines, adequate clinical monitoring in line with clinical guidelines should be envisaged.
Use of biological and biosimilar medicinal products in Slovenia and in Europe
Over the last few years, the use of biological medicines has significantly increased due to the demographic changes and new treatment approaches. In Slovenia, the availability of biologicals is comparable to that of other European countries. However, statistics show that the prescribing of biosimilar medicines in Slovenia and in some other European countries is still relatively low (IQVIA, 2026).
Increased competition between biological medicines has the potential to deliver significant savings, which consequently provide more treatment options for patients and healthcare professionals and ultimately increase the availability of these medicines. It is foreseen that the market of biosimilars will increase in the following years and will be available for different therapeutic areas such as cancer, chronic inflammatory skin diseases, neuromuscular diseases, metabolic diseases, diabetes, neutropenia, growth disorders, osteoporosis, etc. So far, about three and more biosimilars of the same reference product are already available on the European market (EMA: Human, Biosimilars). Therefore, it is essential to strengthen the confidence in biosimilar medicinal products.
it should be noted that so far none of the biosimilars authorized in the EU have been withdrawn from the market or withdrawn for safety or efficacy reasons. In addition, data from a few clinical studies showed that the interchangeability of originator with biosimilar is safe and it is not expected to trigger or enhance immunogenicity ((Kurki, P. et al. (2021); Pinheiro, L.C., (2021); Druedahl, L.C. (2022) ; Barbier, L. (2020) ; Herndon TM. et al., (2023).
It is believed that the active post-marketing surveillance of switch-related adverse events by registries as well as improved adverse event reporting and analysis could provide the necessary safety net and support the interchangeability.
