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Future of Regulatory Safety Assessments

  • Gerd Bode
  • Petra Starck-Lantova
Living reference work entry

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Abstract

Drug development contributes to improve health, duration, and quality of life. Lethal diseases have turned into chronic tolerable conditions, but medical need for many pathological processes continues. Concerns appear that in spite of extensive workload, success of pharmaceutical activity, and included facilitated access to novel drugs, may slow down. The preclinical testing via in vitro and animal experimentation reveals limitations to select the right promising candidates, most likely to be effective in humans and predict undesirable side effects early on.

Therefore, constant efforts are necessary to improve the strategies. Courage needs to be stimulated to leave traditional paths and find new and better ways. This “rethinking” process needs directions to focus on additional options: use of more in silico data, deeper insight via cell cultures or receptor studies, new methods to explore more intensively relevant mechanisms of diseases and pharmacodynamics, more comparative data from different animal models, which species really deliver signals relevant for patients; for this objective, disease models or implementation of human conditions into transgenic animals may be supportive. More rigorous randomized designs of preclinical studies and their blinded assessment may improve reproducible and therefore validated results.

In times of “big data” regulatory agencies, academic and industry researchers (possibly under political pressure) should feel obliged to stop selective publications (only positive effects) but create access also to options to learn from failures. The use of available knowledge (literature, experience, scientific advice) may limit the risks of reducing attrition rates and help to shorten timelines. Discussions with agencies have already facilitated a number of strategies. Examples are ICH guidelines M3 (allowing early access to new compounds for women of childbearing potential) or S 9 (reducing the preclinical development package for patients suffering from tumors).

The purpose of this chapter is to prompt openness and imagination to use new methods, more science, experience, and communication among researchers to the benefit of patients.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Institute of Pharmacology and ToxicologyUniversity Medical CenterGoettingenGermany
  2. 2.The University of Bonn/German Society for Regulatory AffairsBonnGermany

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