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Background: The nonclinical as well as clinical development of orphan drugs is difficult, owing to unknown pathophysiology and the absence of animal models. Both, the U.S. Food and Drug Administration (FDA) Guidance and European Medicines Agency (EMA) Guidelines, for orphan drug development describe non-clinical studies, but lack specific information, such as animal species and study design. Against this background, this study aimed to elucidate efficient methods for evaluating nonclinical efficacy based on a review report of orphan drugs approved in Japan. Results: A total of 184 orphan drugs, including 84 anticancer and 100 non-anticancer drugs, approved in Japan from January 2010 to December 2019 were investigated. Some anticancer drugs progressed to clinical development without distinct efficacy data in nonclinical studies. Patient-derived cells have been used for some drugs due to a lack of established cell lines. Cells used for non-clinical studies were devised for drugs indicated for cancers resistant to prior therapies, tumours with specific amino acid mutations in the target molecules, and solid tumours with specific biomarkers. For some non-anticancer drugs, similar disease animal models and normal animals were used for evaluation, since animal models did not exist. Biomarkers have been used specifically for evaluation in normal animals and as endpoints in some clinical trials. Conclusions: It was possible to evaluate drug efficacy by flexibly designing nonclinical studies according to disease characteristics for potentials orphan drugs. These approaches, which are not described in detail in the EMA Guideline or FDA Guidance, may thus lead to approval. [ABSTRACT FROM AUTHOR]

Monitoring of antimicrobial use is essential in the management of the development and selection of antimicrobial resistance. A variety of indicators has become available to monitor antimicrobial use in human and animal medicine. One of them is an indicator based on defined daily dose (DDD). By using the number of DDDs administered and normalising it by the population at risk of being treated over a defined period, one can estimate the number of treatment days with antimicrobial agents in a population. For veterinary medicine, the European Medicines Agency (EMA) has published the European values of DDD (DDDvet) for food-producing animals. In this study, we defined Japanese defined daily doses for antimicrobial agents (DDDjp) using DDD values that we previously assigned for antimicrobial products approved for use in pigs, cattle and poultry in Japan and compared them with DDDvet values. For the comparison, the quotient of Japanese and European values (QDDD) was calculated and the effect of the administration route and the number of active substances contained in the preparation was investigated. A total of 59 DDDjp values were defined for 43 antimicrobial agents using the data of 276 products approved for use in pigs. Likewise, a total of 55 DDDjp values were defined for 32 antimicrobial agents using the data of 196 products for use in cattle, and a total of 27 DDDjps values were defined for 25 antimicrobial agents using the data of 131 products approved for use in poultry. A comparison was made for 42, 28 and 17 pairs of DDDjp and DDDvet values for antimicrobial agents used for pigs, cattle and poultry respectively. The comparison showed median QDDD value of 0.61 and 0.66 for antimicrobial agents used for pigs and cattle respectively (p<0.01), indicating that the Japanese daily doses are significantly lower than the corresponding EMA values in these species. For the antimicrobial agents used for poultry, no significant difference was observed between DDDjp and DDDvet values with a median QDDD value of 1.15. The difference between DDDvet and DDDjp values and absence of DDDvet values for some antimicrobial agents marketed in Japan indicate that DDDjp rather than DDDvet should be used as the basis for the calculation of antimicrobial use monitoring in farm animals in Japan. [ABSTRACT FROM AUTHOR]

In Japan, maintaining the universal health insurance system has become a major social issue in our rapidly aging society with soaring expense of social security contributions and skyrocketing medical costs, etc. Nowadays generic medicines have become standard therapeutic medicines even in the field of cancer treatment. In terms of cost-effectiveness, biosimilars are expected to enhance patients' access to beneficial treatment and so contribute to patients' quality of life as well as reducing the economic burden and total medical expenses while providing equivalent therapeutic outcomes inexpensively compared to the original biologics. Regarding the approval requirements of biosimilars, unlike generic products, they need a Phase III clinical trial in addition to the characterization study which proves similarity to the originals. Biosimilars have been approved through a review process of an application package which is similar to that of new drugs. However, in Japan, biosimilars have not become standard therapeutic choices yet. Approvals of biosimilars and their prevalence in the medical front have been proceeding in Europe and those products have grown in popularity as standard therapeutic choices. In European countries, the European Medicines Agency, academic societies and governmental authorities in each country have implemented a variety of measures to facilitate use of biosimilars. As part of such efforts, the EMA published a guideline on similar biological medicinal products containing G-CSF in 2006. In overseas ASCO and ESMO have already issued a position paper and statement on biosimilar products. In Japan, the Japan Society of Clinical Oncology recommends the biosimilars in its guideline for acceptable use in 2013. This presentation covers the initiatives for biosimilars in Europe and the US, the situation and the challenges in Japan as well as the activities of the Japan Biosimilar Association. [ABSTRACT FROM AUTHOR]