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Safety of Biologics, Including Biosimilars: Perspectives on Current Status and Future Direction

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Abstract

In recent years, marketing of highly innovative and costly biologics improved the management of high-burden diseases such as autoimmune diseases, cancers, and chronic renal failure. Several widely prescribed biologics have recently lost or will shortly lose their patents, thus opening avenues to the marketing of a growing number of biosimilars worldwide, which are products similar in terms of quality, safety, and efficacy to already licensed reference products, thus allowing for potential savings in pharmaceutical expenditure. Numerous debates about the interchangeability between biosimilars and reference products are still ongoing, owing to concerns about potential immunogenicity raised by switching, which may cause a lack of effect and toxicity. Patients successfully treated with biologic therapy may theoretically receive biosimilars to contain costs, if reference product and related biosimilar are judged as interchangeable. However, the positions of regulatory agencies on the interchangeability and automatic substitution of biologics with biosimilars are very different. The benefit-risk profile of biosimilars has been often questioned by clinicians owing to the limited amount of pre-marketing information on clinical efficacy and safety, despite biosimilarity being based on a comparability exercise with the reference product to gain the biosimilar approval. Nevertheless, after more than 10 years of marketing from the first biosimilar approval in Europe, no proof of differences in terms of the safety profile of biosimilars and originators has been reported. In this context, post-marketing evaluation of both biologics and biosimilars safety profiles through analyses from spontaneous reporting databases and claims databases is crucial. An important issue for the pharmacovigilance of biologics concerns the traceability, indicating the brand name and batch number in spontaneous adverse drug reaction reports, but this requirement is not frequently addressed. This review aims to provide an overview of the characteristics and potential challenges in the safety profile assessment of biologics with a focus on the post-marketing setting.

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Authors and Affiliations

  1. Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via Consolare Valeria, Messina, Italy

    Ylenia Ingrasciotta & Gianluca Trifirò

  2. Unit of Clinical Pharmacology, A.O.U. Policlinico “G. Martino”, Messina, Italy

    Paola M. Cutroneo, Ilaria Marcianò & Gianluca Trifirò

  3. Sicilian Regional Pharmacovigilance Center, Messina, Italy

    Paola M. Cutroneo

  4. Foundation Pharmacy for Hospitals in Haarlem, Haarlem, The Netherlands

    Thijs Giezen

  5. Unit of Rheumatology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    Fabiola Atzeni

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  1. Ylenia Ingrasciotta
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Gianluca Trifirò has participated in advisory boards on biosimilars organized by Sandoz and Hospira; furthermore, he coordinates a pharmacoepidemiology research team at the University of Messina, which receives research grants for projects that are not related to the topic of this paper. Ilaria Marcianò, Ylenia Ingrasciotta, Paola M Cutroneo, Thijs Giezen, and Fabiola Atzeni have no conflicts of interest directly relevant to the content of this article.

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Ingrasciotta, Y., Cutroneo, P.M., Marcianò, I. et al. Safety of Biologics, Including Biosimilars: Perspectives on Current Status and Future Direction. Drug Saf 41, 1013–1022 (2018). https://doi.org/10.1007/s40264-018-0684-9

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