For toxicokinetic (TK) evaluation in non-clinical studies, it is often necessary to use satellite animals in rodents, owing to the volume of blood required for measurement of drugs. However, with the recent increases in the sensitivity of analytical instruments, it is now possible to evaluate TK with a smaller volume of blood by using a microsampling technique. As the application of microsampling can permit the evaluation of TK in the main study animals, it is possible to directly evaluate the relationship between the toxicology data and drug exposure in the same animals, and to reduce the number of animals or their pain, thereby contributing to the replacement, refinement and reduction of animals (3Rs) in research. To accelerate inclusion of this technique in TK studies, the ICH decided, in 2014, to make a Q & A for the S3A guideline, which was finalized in November 2017; the Japanese version was issued in March 2019. This Q & A describes points to consider when applying the microsampling technique for TK evaluation. Microsampling techniques have been used more often in non-clinical studies for applications for investigational new drugs (INDs) as well as new drug applications (NDAs) in Europe and the United States than in Japan. In UK, the National Centre for the Replacement Refinement & Reduction of Animals in Research has established a microsampling working group to share and publicize the knowledge of the industry. In Japan, an AMED research group has been conducting joint research projects on the practical application of microsampling, and its achievements have been evaluated in detail at academic meetings. This review introduces the background to ICH S3A Q & A, outlines the contents, and describes the recent progress in microsampling in Japan and other countries.

ICH S9 guideline provides recommendations for nonclinical evaluations to support the development of anticancer pharmaceuticals in clinical trials for the treatment of patients with advanced disease and limited therapeutic options.“Questions and Answers: Nonclinical Evaluation for Anticancer Pharmaceuticals (ICH S9 Q & As)”has developed to add precise and concrete explanation on issues which have been interpreted differently among regulatory agencies, or between such agencies and sponsors, in the operation of the guideline. In this article, we describe an overview of the ICH S9 Q & As and the process of their development, from the standpoint of regulatory members of the ICH S9 Q & As Implementation Working Group.

The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) is to promote public health through international harmonization of technical requirements that contribute to the prevention of unnecessary duplication of non-clinical studies, and to the minimization of the use of animal testing without compromising safety and effectiveness. A major output of ICH’s work is the development by working groups of harmonized technical guidelines and other work products to support harmonization activities on quality, safety, efficacy and multidisciplinary topics. In case of the safety topics, these activities were progressed on 7 topics by technical working groups〔including expert working groups (EWG) and implementation working groups (IWG)〕from May 2017 to June 2019. Namely, Q & A of ICH S3A (the assessment of systemic exposure in toxicity studies focus on microsampling) and Q & A of ICH S9 (Nonclinical Evaluation for Anticancer Pharmaceuticals) were adopted by the regulatory members of the ICH assembly at Step 4 of the ICH process. The EWG of ICH S5 (R3) (Detection of Reproductive and Developmental Toxicity for Human Pharmaceuticals) and ICH S11 (Nonclinical Safety Testing in Support of Development of Paediatric Medicines) address the comments received during the regional public consultation period. ICH S1 (R1) EWG (Rodent Carcinogenicity Studies for Human Pharmaceuticals) continues its work on drafting revision to the guideline. In 2018, ICH S7B IWG (The nonclinical Evaluation of the Potential for delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals) and ICH M7 (R2) EWG/IWG (Assessment and Control of DNA Reactive Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk) were endorsed by the ICH assembly and started to develop each Q & A.

Pediatric drug development has been an important part of the drug-development process. To support pediatric drug development, pharmaceutical companies will develop a strategy and assess the need to perform juvenile animal studies (JAS). JAS are conducted depending on known information such as clinical context, pharmacology, clinical/nonclinical data, etc., of developing pharmaceuticals on a case-by-case basis. When JAS are judged to be needed, an appropriate study should be designed to address possible safety concerns for the pediatric population. However, lack of harmonization among the regulatory regions on criteria used to determine the need of JAS, and on specific aspects of study design, complexifies the conducting of JAS. In this review, background and current status of JAS are outlined. Key points when judging the need for JAS and designing JAS are introduced based on the current discussion in ICH S11. In addition, current issues of JAS are also discussed.

Since the first successful generation of induced pluripotent stem cells (iPSCs) by Yamanaka et al. in 2007, there has been progress in related research, along with increasing technological advances. Expected applications in drug development include use of human-derived iPSCs for drug safety evaluation and patient-derived iPSCs for pathological analysis, and for exploration and development of therapeutic drugs. Efforts toward practical application are underway, with clinical trials already initiated for some cellular- and tissue-based products using iPSCs. However, iPSC application involves issues requiring special attention in the context of their characteristics. The Pharmaceuticals and Medical Devices Agency has compiled current considerations for iPSC application in drug discovery and regenerative medicine based on published information on iPSC application and our experience with consultations regarding iPSC use for drug development, and for cellular- and tissue-based products. In this review, we present an overview of these considerations to help facilitate further drug development.