As with all other medicinal products, marketing authorisation must be obtained for all biosimilars before they can be marketed. Marketing authorisation is issued once the European Assessment Committee CHMP, in which the MEB is represented, has scientifically assessed the efficacy, safety and quality of the medicinal product.

Biological medicinal products are prepared by using living biological systems. Heterogeneity is inherent to the nature of biological products and their manufacturing process. In addition, the manufacturing process (and thus the finished product) is highly sensitive to changes in the manufacturing process (e.g. preparation, purification and formulation). 

Consequently, two independently developed manufacturing processes for the same biological medicinal product can result in equivalent (=similar) – but never identical – medicinal products. A biosimilar medicinal product will therefore, for all intents and purposes, still exhibit differences with respect to the innovator product. However, this also applies to two biological reference medicinal products which contain the same active substances. 

Because the biological reference medicinal product has already been on the market for several years, information is available that does not need to be collected again. The trials that must be carried out to show that the ‘biosimilar’ is as safe and effective as the innovator product are laid out in legislation. These trials are performed in a step-wise manner, beginning with a comparison of the quality and consistency of the medicinal product and manufacturing process. Comparative studies of medicinal product safety and efficacy are also conducted. These studies must demonstrate that there is no significant difference between the safety and efficacy of the biosimilar medicinal product and the innovator product. 

When the biological reference medicinal product is applied to different conditions, the efficacy and safety of the biosimilar medicinal product must be demonstrated for each condition. This can be done by conducting a clinical study for each indication, but it is also possible to use a well-substantiated argument to show that a study involving one condition also demonstrates efficacy and safety for another condition.

A description of the studies carried out can be found in the public assessment report of the biosimilar medicinal product. This public assessment report is published on the website of the European Medicines Agency (EMA). Section 5.1 of the summary of product characteristics (SmPC) mentions whether a medicinal product is a biosimilar medicinal product. In the case of a biosimilar medicinal product, section 5.1 of the SmPC mentions the studies that have been carried out with the reference medicinal product.

Biosimilar medicinal products are subject to the same manufacturing quality norms as all other medicinal products. The Netherlands Health and Youth Care Inspectorate (IGJ) performs periodic inspections of the manufacturing site(s), as it does for all other medicinal products.

Monitoring following marketing authorisation

The safety of all medicinal products, including biosimilar medicinal products, is continuously monitored after approval. Each company must introduce a system to control the safety of marketed products. The IGJ can also inspect this system.

It is known that biological medicinal products can be immunogenic (i.e. causing an immune response) and that this can have an impact on the product’s efficacy and safety. However, it is difficult – if not impossible – to predict the potential immunogenicity based on non-clinical studies. Moreover, these relatively rare, but severe, adverse events can only be detected in a larger patient population and after long-term use. Extrapolation based on the innovator product data is, of course, also not possible. For biosimilars, the Committee for Medicinal Products for Human Use (CHMP) usually requires one year of immunogenicity data before marketing authorisation is granted. 

For biosimilar medicinal products, just as for every new medicinal product, it is therefore important to draw up a Risk Management Plan and enable proper pharmacovigilance by also fully guaranteeing the traceability (i.e. which patient has been given which medicinal product at what time).

If specific warnings need to be taken into account when using the innovator product, these will likely also apply to the biosimilar medicinal product. Undesirable effects experienced while using the medicinal product can be reported to the Netherlands Pharmacovigilance Centre Lareb. It is important when filing a report to record as many details as possible regarding the applied product.