Biological Medicinal Products
Biological medicinal product is a product, the active substance of which is a biological substance (Directive 2001/83/EC). A biological substance is a substance that is produced by or extracted from a biological source and that needs for its characterisation and the determination of its quality a combination of physico-chemical-biological testing, together with the production process and its control. However, all substances extracted from a biological source are not biological medicinal products, for example antibiotics which are produced in yeast/mold or polysaccharides, which can be accurately analysed and for which there is no viral risk, are classified as chemical medicinal products. The list of biological medicinal products is updated when necessary.
Biological medicinal products include e.g. vaccines, blood products (e.g. coagulation factors), allergens and products manufactured using recombinant technology (proteins, e.g. insulin and antibodies). The newcomers of the group are so-called advanced therapy medicinal products (ATMPs): gene- and cell therapy medicinal products and tissue engineered products.
Biological medicinal products were previously developed mainly for rare diseases, but nowadays more and more of them are directed towards treatment of common diseases like diabetes, arthritis, inflammatory bowel diseases, asthma and cancer. Biological medicinal products are believed to hold significant position in future medication, as already half of the products under development are biological medicinal products.
Supervision of biological medicinal products
The supervision of biological medicinal products has always been under special attention in EU legislation, due to the fact that these products differ from other medicinal products with regards to their composition and manufacturing processes. The active substances of biological medicinal products are often heterogeneous mixtures, because of their starting materials (live cells) and complex manufacturing and purification processes.
The marketing authorization applications (MAA) of biological medicinal products are handled solely through the centralized MA process, which is co-ordinated by the European Medicines Agency (EMA) in London. In addition to pharmacy and pharmacology, the supervision and evaluation of biological medicinal products is based on many other sciences like biochemistry, cell and molecular biology, microbiology, virology and immunology. For the regulation new scientific information is applied on a case by case basis, because the guidelines in this field are not very detailed. The assessment of the quality and manufacturing data of biological medicinal products is centered to Biologics Working Party (BWP) at the EMA, whereas the Committee for Human Medicinal Products (CHMP) has the overall responsibility of the MAA assessment.
Fimea continuously improves its´ know-how for the supervision of biological medicinal products and strives for efficient networking with external experts. For several biological products, the experts from Fimea have participated to classification, scientific advice and assessment of MA applications in centralized and MRP processes, including arbitration processes. The data requirements for MA applications are described in Directive 2001/83/EC, yet there are additional, special requirements for certain products, depending on their starting materials. For example, for products containing blood or other human tissues/cells specific EU requirements have been adopted in 2003 and 2004, respectively. Fimea experts have often played central roles when EU guidelines have been developed for biological and biotechnological products, the guidelines can be found from EMA website.
Biological and especially biotechnologically procudes medicinal products are highly expensive when compared to traditional remedies. In 2003, a mention about biosimilar products was included into the EU legislation with the aim to control the increased cost pressure caused by the biological medicinal products. For biosimilar products the marketing authorization is partly based on an original biological medicinal product, for which the data and patent protection are expired
Biosimilars, however, diverge from common generic products in that their marketing authorization requires more extensive studies than only quality and bioequivalence studies. This is due to the above mentioned heterogeneity of biologicals, the analysis and control of which requires several analytical methods. The Biosimilar Working Party (BMWP), which has also experts from Fimea, is responsible for the guidance for these products.
Advanced Therapy Medicinal Products
The Advanced Therapy Medicinal Products (ATMPs) include gene therapy and somatic cell therapy medicinal products and tissue engineered products, for which the starting materials involve genes and their vectors (viruses, plasmids) and viable cells/ tissues. Regulation (1394/2007/EC ) for ATMPs came into force in EU in 2009 and with that the centralised MA process became mandatory for these products. ATMPs can also contain medical devices (e.g. structural components, matrices) and in such cases they are considered as combination products.
The EMA´s Committee for Advanced Therapies (CAT) is responsible for the assessment of MAAs of ATMPs together with CHMP. Along with the regulation the deficitions of ATMPs were revised and Directive 2001/83/EC was renewed with regards to the technical requirements of these products (implementing directive 2009/120/EC). In addition to evaluation of MA applications, the CAT gives recommendations concerning classification of ATMPs and evaluates quality and non-clinical studies of ATMP certification applications. The guidelines for classification and certification can be found on the CAT webpage, as well as agendas and minutes of the monthly CAT meetings
Outside of the ATMP regulation have been left ATMPs that are produced under a national manufacturing license (so-called hospital exemption, article 28). This manufacturing is regulated by article 15c of the Finnish Medicines Act and it requires a license from Fimea. More information about the hospital exemption in Finland can be found at Fimea’s website.