When asked whether regulators would accept data in lieu of some data to support FIH dosing, 55% of participants were sceptical, pointing toward the need for the scientific community to generate convincing data on the validity of models for human risk assessment. prediction and the therapeutic mAb development process, while reducing and refining animal use simultaneously. In 2014, to engage in open discussion about the challenges and opportunities for the future of mAb development, a workshop was held with over 60 regulators and experts in drug development, mechanistic toxicology and emerging technologies to discuss this issue. The workshop used industry case-studies to discuss the value of the studies and identify opportunities for technologies in human safety assessment. From these and continuing discussions it is clear that there are opportunities to improve safety assessment in mAb development using nonanimal technologies, potentially reducing future attrition, and there is a shared desire to reduce animal use through minimised study design and reduced numbers of studies. studies. The 60 participants included current FDA and European Union (EU) regulators and representatives from the pharmaceutical, biotechnology and contract research industries. A selection of current state-of-the-art techniques were showcased and discussed with a view to how these could be applied either now or in the future to improve the safety assessment of mAbs. Although, it was recognized it may be some time before any of these can be used successfully for decision-making in drug development, the workshop provided Scrambled 10Panx a unique opportunity to mine the vast knowledge and Scrambled 10Panx experience Scrambled 10Panx of this group to gain a consensus perspective on a future vision for safety assessment in mAb development. This paper provides an overview of the discussions that began at the workshop, descriptions of real-life industry case studies with consideration of the value of the and studies, and a plan for future work developed by the authors based on the output of the workshop and recent developments in the field. The workshop Emerging technologies The most recent estimated figure for the cost of getting a drug to market is Scrambled 10Panx almost $2.6?billion19 and between 2008 and 2010 productivity of the pharmaceutical industry was at an all-time low despite the introduction of the first wave of biotechnology derived products in the 1990s. There is some recent evidence that R&D productivity has turned a corner and the industry is sustainable again.20,21 However, attrition, which may be due to lack of efficacy as well as lack of translational safety, is still a huge problem, costing an estimated $1.4?billion per drug.19 For mAbs, the lack of cross-reactivity in rodents may contribute to attrition as there are limited opportunities to study drug candidates in rodent pharmacology models. It is critical for the industry to reduce attrition in order for the increase in productivity to continue. Many technologies are currently being used to reduce attrition in candidate screening for both efficacy and safety, including stem cells, cardiac assays, and models. However, many of these are being used for small molecules, often to assess off-target toxicity, rather than for the screening of biotherapeutics.22 One reason might be that such technologies are not relevant for mAb development because off-target toxicity rarely occurs and the toxicity is primarily related to specific on-target pharmacology. If this is true, the question remains as to whether these or similar technologies could Scrambled 10Panx be modified or developed to address questions that are more suited to biotherapeutics and, if so, how? Perhaps such technologies will need to be more case-specific, dependent on the binding target of the product. Emerging technologies with possible relevance to biotherapeutic development were selected for discussion at the workshop Rabbit Polyclonal to GIT2 and included: 1) organs-on-chips types of technologies; 2) systems pharmacology and modeling; 3) human immune models, as showcased by VaxDesigns’s MIMIC? technology;23 and 4) human pluripotent stem cells as a tool for developmental biology, as showcased by Stemina Biomarker Discovery’s devTOX? discovery assay.24 The name organ-on-a-chip refers to microfluidic cell culture devices that contain continuously perfused chambers inhabited by living cells arranged to simulate tissue- and organ-level.