Although regulatory science has been recognized as an important field in the area of pharmaceutical regulation, it may be still immature and is likely to evolve further as science itself advances with an increasing accumulation of knowledge and experience. In real-life situations, the strength of evidence for each set of data and information used for regulatory assessment varies widely. Indeed, inconsistent results are not uncommon. Scientific, non-biased, and objective assessment based on all of the available data and information may pinpoint the truth and determine the value of science to society in advancing public health. From this perspective, regulatory science can be viewed as important for finding practical and up-to-date solutions for issues where there is a degree of scientific uncertainty and limitations. As such, regulatory science is invaluable for improving pharmaceutical regulation. The combined involvement of experts across a wide range of disciplines engaged in medical, pharmaceutical, statistical and technological sciences, as well as economics, jurisprudence, education, and other disciplines will be important in increasing research activities in regulatory science. Discussing each issue from various perspectives will be crucial in finding the best solutions. Continuous effort at the global level will be necessary for further developments of "regulatory science" that can be applied to various real-life issues in society.
Since the genetic, metabolic, and physiological characteristics of nonhuman primates (NHPs) are very similar to those of humans, NHPs serve as excellent animal models for biomedical research. Recent advances in genetic engineering and assisted reproductive technologies related to NHPs have enabled the development of genetically modified NHP models for human disease related studies. The common marmoset (Callithrix jacchus) is a useful laboratory animal model that is suitable for generating genetically engineered models due to its unique reproductive characteristics, such as prolific breeding, relatively short gestation period and small body size. Genetically modified marmoset models may be used as critical intermediaries to accelerate the progression of various conceptual technologies and therapeutics from the basic research stage to the clinical application stage. The last decade has witnessed the growth of genetic engineering technologies pertaining to NHPs as well as new gene modification technologies, such as gene editing. Such technological advances have enabled the development of genetically engineered NHP disease models for translational research.
In drug development studies, various in vitro model systems (such as Caco-2 cells and intestinal microsomes) are widely used for evaluating intestinal pharmacokinetics and toxicological properties of drugs, including the rate of drug absorption, drug metabolism, and extent of mucosal damage. However, these approaches have limited accuracy in predicting intestinal availability and toxicity. To overcome these problems, new approaches have been recently developed to generate intestinal epithelial cells and organoids that are derived from induced pluripotent stem (iPS) cells, which have shown great potential for use in drug development studies. In this review, we summarized our research regarding intestinal epithelial cells and organoids generated from human iPS cells. We demonstrated that intestinal epithelial cells derived from human iPS cells exhibit drug-metabolizing enzyme activities, drug transporter activities, and cytochrome P450 inducibility. We speculated that drug-induced intestinal mucosal damage in derived epithelial cells can be evaluated. Moreover, intestinal organoids derived from human iPS cells were found to contain various intestinal cell types and develop apical-basal polarity. The differentiated organoids have intestine-like structures with desired pharmacokinetic attributes and barrier functions. Intestinal epithelial cells and organoid tissues derived from human iPS cells show great potential to be more widely used in drug development studies, including pharmacokinetic studies, toxicological evaluations, drug screening, and studies on intestinal bowel disease models.
Dog is an important animal model for translational research to study human diseases. This translational research includes identification of causative genes for shared diseases with humans, identification of new drug targets for the treatment of patients with monogenic diseases, canine clinical trials conducted before and parallel with human clinical trials, and intervention research in healthy dogs. For future research, I propose two important considerations. First, knowledge of the genetic epidemiology of diseases in each breed of dog used is indispensable to precisely identify dogs with the best potential in translational research. Second, research in dogs has a significant potential to expand actionable disease treatment to patients with genetic risk of disease. Translational research in dogs can help enhance human medical sciences in addition to veterinary medicine.