Risk Assessment: Traditional and Novel Approaches to Assess and Manage Risks

Risk assessment is a complex process intended to protect human health by identifying drug-related hazards; determining dose-response relations for a product within relevant biological systems; and assessing exposure levels to characterize potential risks. These assessments may be conducted via traditional frameworks using data from in vitro and in vivo studies, as well as novel frameworks using pharmacokinetic and pharmacodynamic model-based prediction. Data used to assess risks are typically collected under conditions that mimic, as closely as possible, the clinical context in which a given product is intended for use. Across the mentioned frameworks, risk assessment must be based on clinically relevant information and include exposure data.

Risks may be characterized by evaluating the mechanism/mode of action, onset and offset and incidence of clinically relevant hazards. Traditional frameworks put risks into perspective based on the target organs of toxicity identified and the exposure levels at which hazards occurred. The exposure levels at which hazards occurred are used to identify the most sensitive species, which is typically deemed the most relevant species, unless proved otherwise.

Modeling approaches enable extrapolation of data from preclinical species to humans using established physiological differences. These approaches also allow prediction of hazard and exposure in scenarios not explicitly measured in preclinical studies. Modeling frameworks can be incorporated at a very early stage in the development pipeline and can also assist in determining which set of preclinical studies would be most clinically relevant.

Although these frameworks are intended for characterizing and putting potential risks into perspective, each is critical in managing potential clinical risks within relevant contexts to ensure patient safety.

Join the discussion on traditional and novel risk assessment frameworks, the advantages and disadvantages of these frameworks and explore case studies and perspectives on current and future challenges related to them.

Speakers

Marcus Delatte, Vice President, Regulatory Strategy, Consulting, Allucent

Dr. Marcus S. Delatte, PhD, completed a fellowship at the Harvard Medical School/McLean Hospital prior to working over 11 years at the US Food and Drug Administration (FDA) as a Senior Pharmacology/Toxicology Reviewer. In that role, Marcus gained expertise in regulatory affairs, as well as risk assessment and management of small and large molecule products. His FDA experience involved managing over 264 IND and 30 NDA applications; advising sponsors on the adequacy of the design and results of pharmacology, safety pharmacology, general toxicology, genetic toxicology, reproductive and developmental and carcinogenicity studies; in addition to training and supporting regulatory staff. These experiences prepared him to transition into consulting, where he continues to serve customers across the world and to grow his expertise via engagement with client projects and thought leadership projects. As a Vice President of Regulatory Strategy, he serves in multiple roles that include project lead, nonclinical expert and regulatory strategist.

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Laura Erwin, Regulatory Scientist, Consulting, Allucent

Dr. Laura Erwin holds a doctorate degree in pharmacology from LSU Health Sciences Center and received post-doctoral training from Harvard Medical School and Mclean Hospital. She has presented her work at conferences around the country, published on abuse liability and discussed scheduling issues and concerns with senators and representatives on Capitol Hill. Her extensive research background in preclinical pharmacology has aided her in assessing, communicating and managing the risks related to various types of products being developed (e.g., small molecules, biologics and devices). In her current position as a Regulatory Scientist, she successfully helps companies create realistic clinical trial management plans and product development strategies that fulfill regulatory concerns, as well as fulfilling all regulatory concerns relating to FDA meeting preparation, IND submission, orphan drug designation and abuse liability assessment plans.

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Manushree Bharadwaj, Senior Pharmacokineticist, Clinical Pharmacology, Modeling & Simulation, Allucent

Dr. Manushree (Manu) Bharadwaj, DVM, PhD (biomedical sciences) has over four years of experience in the world of pharmacokinetics (PK) and pharmacodynamics (PD). At Allucent, she performs PK/PD evaluations of clinical and non-clinical studies of small and large molecules. She also held a clinical pharmacologist position in the field of veterinary drug development. She has experience in reviewing animal drug applications for drug safety, effectiveness and bioequivalence at the Center for Veterinary Medicine, US FDA. She was a postdoctoral fellow at National Toxicology Program Laboratories, National Institute of Environmental Health Sciences where she studied the effects of industrial chemicals such as plasticizers on embryonic and fetal development. She enjoys performing PK analysis and answering challenging PK questions.

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Angela Jeong, Fellow Intern, Clinical Pharmacology, Modeling & Simulation, Allucent

Angela received her PharmD and PhD in experimental and clinical pharmacology at University of Minnesota-Twin Cities. Her thesis focused on studying the role of protein prenylation and downstream signaling pathways in the pathogenesis of Alzheimer’s disease cell and animal models. Angela then joined UNC-Allucent Pharmacokinetics and Pharmacodynamics (PKPD) Postdoctoral Fellowship, during which she worked on various projects including physiologically-based pharmacokinetic modeling (PBPK)-based dose optimization in children with obesity as well as hepatobiliary disposition and clearance modeling of compounds using preclinical data. Angela is currently in the 2nd year of her fellowship. Her passion lies in PBPK and quantitative systems pharmacology (QSP) modeling-guided drug development.

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