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Ther Innov Regul Sci. 2019 May 13:2168479019843514. doi: 10.1177/2168479019843514. [Epub ahead of print]

Shared Learnings on the New EMA First-in-Human and Early Clinical Trial Guideline: Proceedings From a DIAlogue Session at DIA Europe 2018.

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1 Section on Pharmacology, Toxicology and Kinetics, Medicines Evaluation Board, Utrecht, the Netherlands.
2 Clinical Pharmacology-San Diego, Eli Lilly and Company, Indianapolis, IN.
3 Federal Agency For Medicines and Health Products, Brussels, Belgium.
4 Regulatory Affairs, Novartis Pharma, Basel, Switzerland.
5 Clinical Trial Unit, Federal Institute for Drugs and Medical Devices, BfArM, Bonn, Germany.
6 Drug Safety Research and Development, Pfizer, INC, Cambridge, MA.
7 Medical Products Agency, Sweden.
8 AstraZeneca, Paris, France.
9 Citoxlab, Evreux, France.
10 Preclinical Safety, Novartis Pharma, Switzerland.
11 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
12 Clinical Development, Vertex Pharmaceuticals Incorporated, Boston, MA.
13 Department of Pharmacology, Universidade de Lisboa, Lisboa, Portugal.
14 NDA Advisory Board, UK.
15 Global Medical Affairs, Eli Lilly and Company, Indianapolis, IN.
16 Preclinical Safety, Novartis Pharma, Basel, Switzerland.


The EU is a member of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), and therefore adopts the ICH Guidelines, including the ICH M3 Guideline on Nonclinical Safety Studies. Following the 2016 incident in France with BIA 10-2474, and in light of the substantial evolvement of how early clinical development has been undertaken during the last 10 years, for example, conducting integrated (FIH) studies that include multiple parts (eg, single ascending doses, multiple ascending doses, food effect), EMA decided to update the existing 2007 FIH guideline. The key revisions to the 2007 guideline, now titled "Guideline on Strategies to Identify and Mitigate Risks for First-in-Human and Early Clinical Trials With Investigational Medicinal Products," include additional information. The revision reinforces the importance and impact of pharmacologic data, which supports the intended efficacy of the compound, risk assessment, and protocol design. The updates, effective February 2018, are intended to provide additional guidance and clarity for Sponsors developing FIH and early phase clinical research programs, and ultimately support subject safety. At the 2018 DIA Europe Annual Meeting in Basel, Switzerland, European regulators, industry representatives and academics convened a DIAlogue Session on April 17 to discuss how the revised 2017 guideline is being applied, and to establish recommendations for its application. Using two case studies as examples, the session participants discussed the nonclinical and clinical considerations for applying the newly revised recommendations, and interacted with a panel including regulators and industry representatives. The proceedings from this session reflect practical considerations for the implementation of the revised guideline.


EMA Guideline; clinical trial; first in human; risk assessment


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