Preclinical Development – Biomolecular
2019 PharmSci 360
William Slikker, Jr., Ph.D.
National Center for Toxicological Research/Food and Drug Administration, USA
Emerging Technologies for Regulatory Science: How Can FDA Help?
Emerging technologies are playing a major role in the generation of new approaches to assess the safety of both foods and drugs. However, the integration of emerging technologies in the regulatory decision-making process requires rigorous assessment and consensus amongst national and international partners in various research communities. The need for advanced approaches to allow for faster, less expensive and more predictive methodologies is becoming increasingly clear. In addition, the strengths and weaknesses of each new approach need to be systematically examined. In pursuit of the goal to simulate a human, at least in terms of chemical effects, safety evaluation, and the practice of regulatory science, a system of cells or tissue may be examined under strict criteria to reflect the human condition. These “Human-on-a-chip” and “human organ construct” microphysiological systems (MPS) are an emerging technology that has the potential to correlate in vivo with in vitro and simulate human organ systems. Even though the use of human cells may be an enormous advantage because there is no need to extrapolate across species, there is the requirement that different cell types be characterized in terms of developmental stage and functional capacity. Other approaches including minimally-invasive imaging approaches and liquid biopsy have also been developed and are gaining acceptance as emerging technologies that have an impact as innovative biomarkers for safety assessment.
The development and validation of a whole series of important biomarkers for toxicity has greatly streamlined the process and shortened the time involved in new drug development and approval. These biomarkers are qualiﬁed for a very speciﬁc context of use and have often detected significant toxicity of lead compounds in preclinical stages of testing rather than Phase 2 of clinical trials saving enormous amounts of money (often three orders of magnitude in dollars spent) and, more importantly, prevented adverse effects, suffering, and possible deaths in clinical trials. Finally, the astounding advances in various types of imaging have not only opened a new set of opportunities to evaluate toxicity, noninvasively in a multitude of organ systems in living organisms but has given a novel insight into fundamental aspects of human biology and physiology. The partnership between the science of predictive toxicology and legislative regulatory initiatives has contributed greatly to the advancement of each of these activities and this complementary relationship has contributed considerably to the enhancement of quality of life.