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The biggest differences between the development of a biosimilar and a generic medicine lie primarily in the preclinical and clinical stages.
The biggest differences between the development of a biosimilar and a generic medicine lie primarily in the preclinical and clinical stages. Unlike with classical generics, in order to obtain marketing authorisation, biosimilars manufacturers must submit animal data and data on efficacy in patients. The exact requirements depend on the product. For epoetins, for example, two clinical efficacy trials are expected, but for G-CSF induction of leukocytes in a volunteer study is considered adequate. Another important part of the biosimilar submission process is the similarity exercise, i.e. where the biosimilar must prove to be sufficiently similar to the original product in terms of quality, safety and efficacy.
The European regulations from the European Medicines Agency (EMA) have not set any specifications concerning the differences that are acceptable between the biosimilar and the original product. Differences will always be found, for instance in the glycosylation between two epoetin products, but if the clinical data show that these differences are not clinically important, the EMA will accept them.
In practice biosimilar manufacturers have analysed the original product for a number of years to get data on the batch-to-batch variation and their specifications are set based on the quality of the original. The monograph included within the European Pharmacopeia is another source of specifications and quality attributes.
In Utrecht University we are currently analysing the quality of biosimilar epoetins and we find these comparable and sometimes even higher in quality than the originals.
In general, clinicians prefer not to switch patients from one biologic to another. This is reinforced by statements by the EMA, which state that a biosimilar authorisation does not imply that the product is exchangeable with the original as is the case with generics. In addition there are concerns about the long-term safety of biosimilars, because they have only recently been introduced; clinicians want to wait for a couple of years until the safety is established. As such, all biosimilar companies are required by the EMA to study long-term safety post-marketing. Further, to make the biosimilar treatment traceable, substitution without the consent of the treating physician is discouraged and even made illegal in some European countries.
Although there is no specific pharmacovigilance programme in place for biosimilars in Europe, as for any other drug, biosimilars manufacturers are required to submit a risk management programme, which includes a comprehensive pharmacovigilance programme. Although the biosimilar companies run these programmes, the EMA first evaluates the capacity of the companies to comply with pharmacovigilance demands.
Finally, although the key selling point of a biosimilar is its low price, this may not be deemed sufficiently lower than the originator in order to stimulate its use.
Huub Schellekens is Professor in the Department of Pharmaceutical Sciences and Innovation Studies at Utrecht University, The Netherlands.