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Preclinical Cardiovascular Safety Evaluations of Biologics

Optimizing the Approach and Follow-Up

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Abstract

Standard therapeutic agents (STA) are usually relatively small and simple molecules, which are synthesized as highly pure and consistent molecules. However, their target specificity can be low so that there is a liability for side effects at non-targeted receptors, enzymes or ion channels. Alternatively, highly specific and targeted small molecules can elicit cardiovascular liabilities due to their target-based effects. As a result of their long existence in pharmaceutical practice, their safety evaluation is fairly well standardized and their potentially promiscuous, non-specific actions mandate broad evaluations.

Biologics include a wide variety of products, ranging from relatively small synthesized polypeptides, which are also highly consistent, to very complex products, the composition of which may vary widely between production batches and sources. Biologics are usually highly specific for a single target, so that side effects at other targets are very rare. Their toxicities are more related to immune systems and to infection complications than to cardiovascular repercussions.

The standard preclinical cardiac safety evaluations, derived from experience with STA, are frequently not appropriate or warranted for the evaluation of biologics. Indeed, because of the specificity of such biologic products, smaller test batteries than the ones needed for STA may be sufficient. However, because of the potential variability in composition of biologics between production batches and sources, evaluations of such products needs to be performed more frequently than for uniformly produced STA.

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Acknowledgements

The authors have both acted as consultants for various pharma companies. No sources of funding were used to prepare this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this article.

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Authors and Affiliations

  1. Department of Pharmacology, Catholic University Leuven, Leuven, Belgium

    Luc Hondeghem

  2. PharmaConsulting, Beerse, Belgium

    Fred De Clerck

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  1. Luc Hondeghem
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  2. Fred De Clerck
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Correspondence to Luc Hondeghem.

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Hondeghem, L., De Clerck, F. Preclinical Cardiovascular Safety Evaluations of Biologics. BioDrugs 26, 275–282 (2012). https://doi.org/10.1007/BF03261886

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