Guiding principles for biosimilars development

Biosimilares/Investigación | Posted 21/02/2014 post-comment

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In contrast to chemically synthesized small-molecule drugs, biologicals have complex structures of high molecular weight. Therefore, even small changes in the production processes may lead to differences in the final product. The manufacturers of the originator product are not required to disclose their manufacturing process after the patent expiry. This gap in knowledge increases the probability of introducing changes in the manufacturing process of biosimilars, making producing an identical copy of a biological virtually impossible. Indeed, even different batches of the same originator biological may show a certain level of heterogeneity.

For these reasons, Torres and co-authors outline seven principles that they believe should guide the development of biosimilars [1]:

For a biosimilar to be considered ‘similar’ to an originator biological according to the current EU regulatory framework it should undergo all preclinical and clinical steps of the development programme.
Indications should not be extrapolated to the originator’s other indications without prior minimal efficacy and safety demonstration in the proposed indications.
Biosimilars should be evaluated in clinical trials specifically designed for this same indication, since bioequivalence does not necessarily implicate therapeutic equivalence.
Immunogenicity is a primary safety concern for all biologicals; therefore, the investigation of anti-drug antibodies should be a component of clinical trials involving biosimilars.
The automatic substitution of an originator biological for a biosimilar or vice versa should be considered a change of therapeutic and should not be practised without the prior knowledge and consent from the prescribing clinician or without informing the patients. The authors also consider that automatic substitution may compromise the pharmacovigilance programmes.
The biosimilar should have a specific naming procedure in order to distinguish easily between biologicals. This process will allow the healthcare professionals to accurately track the prescribed therapeutic and link the adverse effect to a specific product.
Implementation of post-marketing surveillance programmes for biosimilars, to collect safety data and detect potentially meaningful rare adverse effects, is essential.

Despite the authors’ opinions on extrapolation, automatic substitution and naming of biosimilars, all of which have been regarded as barriers to biosimilars uptake, they state that they are ‘favourable to the development of biosimilars … provided these products follow the highest quality standards in terms of production and development’.

Regarding extrapolation, the European Medicines Agency has stated that ‘if clinical similarity can be shown in a key indication, extrapolation of efficacy and safety data to other indication(s) of the reference product may be possible’ under certain conditions [2]. While advocates for a common name for biosimilars are concerned that there could be the possibility of overdosing or misdoing if different names were used, as a patient could inadvertently be prescribed two versions of the same biosimilar [3].

Conflict of interest
The authors of the research paper [1] have allserved as speakers and on the Advisory Boards of originator biologicals companies.All authors have alsoparticipated in clinical trial andobservational studies funded by originator biologicals companies. For full details of the authors conflicts of interest see [1].

Editor’s comment

Readers interested to learn more about biosimilars development are invited to visit www.gabi-journal.net to view the following manuscripts published in GaBI Journal:

Promoting access to biosimilars: a public−private partnership model for biosimilar development in underserved populations

Statistical considerations for the development of biosimilar products

If you are interested in contributing a research paper in a similar area to GaBI Journal, please send us your submission here.

Related articles

Use of biosimilars in Europe

EMA publishes concept paper on extrapolation

References

1. Torres T, Filipe P, Selores M. Impact of biosimilars in psoriasis treatment. Acta Med Port. 2013;26(6):646-8.

2. GaBI Online - Generics and Biosimilars Initiative. Efficacy, extrapolation and interchangeability of biosimilars [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Feb 21]. Available from: www.gabionline.net/Biosimilars/Research/Efficacy-extrapolation-and-interchangeability-of-biosimilars

3. GaBI Online - Generics and Biosimilars Initiative. Calls for biosimilars to have same INN at WHO meeting [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2014 Feb 21]. Available from: www.gabionline.net/Biosimilars/General/Calls-for-biosimilars-to-have-same-INN-at-WHO-meeting

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