A biosimilar medicinal product is a product that has been developed in such a way as to be highly similar to a biological medicinal product already authorised in the European Union (EU). The existing biological medicinal product is considered the reference product or original medicinal product. After the patent and the exclusivity period of the reference medicinal product has expired, a biosimilar medicinal product is permitted to enter the market.
“Highly similar” means that the biosimilar medicinal product and its reference medicinal product are essentially the same, although their active substances may contain slight differences. These slight differences are due to the fact that the active substances are usually large and complex molecules, and they are produced by living cells.
Production processes are very sensitive to modifications (preparation, purification, formulation, etc.). Two production processes developed independently for the same biological medicinal product may therefore result in equivalent medicinal products, but never identical medicinal products.
However, any differences between the biosimilar medicinal product and its reference medicinal product must be kept within strict limits in order to guarantee that both products work identically. A biosimilar medicinal product can only be approved when it has been confirmed with certainty that its variability and any differences compared to the reference medicinal product will not have any significant effect on the quality, safety or effectiveness of the biosimilar. This is why detailed clinical trials and an in-depth comparative study must be carried out to demonstrate the equivalency between the medicinal products in terms of quality, safety, effectiveness and biological activity.
Furthermore, several biosimilars may exist for the same reference biological medicinal product but, given the complexity of their nature, each biosimilar must be subject to an entirely separate comparison with the reference medicinal product.
Why make biosimilar medicinal products?
Biological medicinal products are complex, which means their development can be very long and costly. Such restrictions may limit patient access to these medicinal products and form an obstacle to their coverage through healthcare systems. Biosimilar medicinal products can mitigate these problems for two main reasons.
- The development of biosimilar medicinal products relies on scientific knowledge obtained through the reference medicinal products. Consequently, not all of the clinical trials carried out on the reference medicinal product need to be repeated.
- When introduced to the market, biosimilar medicinal products drive down the INAMI cost of the reference medicinal product, and, in doing so, offer significant savings to the healthcare system. Furthermore, since 1 April 2018, the biocliff principle applies. This means that all legal price reductions that have yet to be applied will be applied at the same time, to both the reference biological medicinal product and to the biosimilar medicinal product.
More information about the biocliff principle and the “Cheap prescription” measure, which specifically discusses biosimilar medicinal products, is available on the INAMI website.
How are biosimilar medicinal products available in Belgium developed and authorised?
Biological medicinal products, including biosimilar medicinal products, are authorised at European level. In the European Union, marketing authorisation (MA) applications must be subject to a centralised authorisation procedure through the European Medicines Agency (EMA). The European Commission takes decisions on the approval of these medicinal products based on scientific opinions issued by the EMA. The resulting marketing authorisation is valid in Belgium and in all other European Union Member States.
From a legislative standpoint, biological and biosimilar medicinal products are subject to European Directive 2001/83/EC relating to medicinal products for human use. The concept of a biosimilar medicinal product was added in 2004 and the EMA drew up specific European guidelines on marketing authorisations for biosimilar medicinal products in 2006. That same year, the European Commission approved its first biosimilar medicinal product.
The data required for an MA for biosimilar medicinal products in the European Union is not exactly the same as for reference biological medicinal products. However, the same high quality, safety and effectiveness standards apply.
If the reference biological medicinal product is not required to follow the centralised procedure, its biosimilar medicinal products may be authorised through other authorisation procedures: national, mutual recognition or decentralised.
As is the case for any medicinal product, before approval can be granted the benefits of the biosimilar product must be shown to outweigh its risks. This process requires a large amount of data, in particular regarding its purity, its manufacturing and its mode of action. Given that the reference medicinal product will have already been approved for several years in the EEA and its clinical benefit has already been established, certain research carried out for the reference medicinal products does not have to be repeated for biosimilar medicinal products.
At this stage, the evaluation of a biosimilar medicinal product primarily lies in the comparison between the biosimilar and the reference medicinal product to prove that there is no significant therapeutic difference or, in other words, to prove their biosimilarity.
Comparisons are carried out progressively, beginning with detailed laboratory trials, comparing the structure and function of the medicinal products, and continuing with comparative clinical trials. The concept and comparison methodology are discussed in detail in the EMA’s guidelines. The quantity and scale of comparative clinical trials, in particular, are determined by the results of the initial stages of the process and the guidelines.
When the equivalent nature of the biosimilar to the reference medicinal product has been proven for an indication, an extrapolation of other indications can be determined using appropriate scientific justification.
Once the EMA has completed an in-depth scientific evaluation of their quality, safety and effectiveness, the biosimilar medicinal products can be approved by the European Commission for placement on the market throughout the whole European Union. Their availability in Belgium then depends on the company’s decision to commercialise the medicinal products on the Belgian market.