Biosimilars in the EU have to undergo a strictly regulated comparability exercise against the reference medicinal product on the physicochemical, analytical, functional, non-clinical and clinical level. Only if a biosimilar is a close copy of the reference medicine will it be approved as a biosimilar. Despite this fact, however, ethical issues have been raised on the use of granulocyte colony-stimulating factor (G-CSF, filgrastim) in healthy volunteers by the European Group for Blood and Marrow Transplantation (EBMT) and the World Marrow Donor Association (WMDA).
The argument proposed by EBMT and WMDA is that healthy donors do not have any benefit from donating bone marrow and should therefore receive biosimilar filgrastim only when it has been tested in a clinical study in this particular setting (to confirm its safety). This viewpoint has been put forward due to the fact that this indication was obtained by extrapolation of clinical data rather than by a dedicated clinical study, and according to the opinion of EBMT and WMDA ‘unexpected toxicity’ could occur. However, what this unexpected toxicity might be is not made clear and is somewhat surprising considering the fact that biologicals mostly have target-mediated toxicity (known from the reference product), and unspecific toxicity would very likely be picked up already in non-clinical and clinical studies before approval. Impurities, which may be able to elicit such unexpected toxicity are tightly controlled in biosimilars, as is the case for any other biological, otherwise a biosimilar would not be authorized in the EU, and thus quality concerns are not substantiated.
A bioethicist’s view
Bioethicist Dr Carlo Petrini when considering the question: what is the key ethical problem posed by biosimilars, finds that the weight of each problem will vary according to individual cases and that ‘the single most important issue is safety’, and ‘the well-being of the individual must be the priority consideration’.
In the case of G-CSF use in healthy donors Dr Petrini suggests that the ethical questions raised include that:
i) the person being treated with a biosimilar product is not the person for whose therapeutic benefit the treatment is administered
ii) there could be concerns that a biosimilar G-CSF may be associated with greater risks than a brand-name product
iii) the main reason for using a biosimilar G-CSF is economic (the cost to the healthcare service will be lower than in the case of a brand-name drug).
These points suggest that biosimilars are approved purely in order to save money for the society, without appropriate knowledge of the safety consequences and thus putting individuals at risk. However, this would then raise ethical questions about the regulatory approval, not the product’s safety.
Concerning safety, regulatory authorities approve biosimilars based on the fact that their efficacy and safety are comparable to those of the reference product. With respect to cost, a cheaper product does not mean that this is a lower quality product. Biosimilars are subjected to the same stringent regulations post-approval as brand-name biologicals when it comes to quality. This leaves only individual risk, which Dr Petrini admits ‘is complex and there are no universal solutions’.
A clinican’s view
Dr Kalle Hoppu is of the opinion that ‘the ethical questions are not different whether a biosimilar, or an innovator biological product, or a small molecule medicinal product is given’ to a patient. For Dr Hoppu the possibility that there are unknown clinical safety issues associated with the use of authorized biosimilars is a research question, not an ethical question.
There is no evidence that the benefit–risk ratio of biosimilars authorized after successfully passing the regulatory authority’s ‘comprehensive comparability exercise’ would be notably different from that of the originator biological during their life cycle. It is also important to note, that the comprehensive comparability exercise requirement is not limited to quality and safety, but also covers efficacy.
Editor’s comment
Readers interested to learn more on the ethics of biosimilars are invited to view the Letters to the Editor published in GaBI Journal.
If you are interested in contributing a research article in a similar area to GaBI Journal, please send us your submission here.
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Source: www.gabionline.net
