Vaccines are one of the most successful stories in public health in human history. Currently, immunisation averts about 2.5 million deaths every year in the world. To obtain appropriate vaccination is one of the fundamental elements of the human rights on health and is regarded as the responsibility for citizens, communities and governments. Vaccines used for the national immunisation programmes are generally safe and effective when appropriately used. However, vaccination is never zero-risk as any pharmaceuticals and effective vaccines may produce some undesirable side effects. The success of national immunisation programme needs the public's confidence in vaccines, by monitoring risk-benefit balance of vaccines and providing relevant information through pharmacovigilance activities. Pharmaceuticals including vaccines achieve maximum advantage when they are appropriately used based on the sound understanding of their risks and benefits. Pharmacovigilance is defined by the WHO as “the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem” and essential for accurate evaluation of risk-benefit balance of pharmaceuticals. The WHO pursues actions to increase vaccination coverage and aims to spur research and development of Dengue and Malaria vaccines. In addition, the elapsed time between introduction of new vaccines in developed countries and in developing countries is being shortened, and technical cooperation facilitate local manufacture of vaccines in developing countries. This results in increasing immunisation rate and administration of various vaccines including relatively new vaccines on a global mass scale. Under such circumstances with increasing importance of vaccine pharmacovigilance more than ever, the article outlines the global movements on vaccine pharmacovigilance, mainly focus on the WHO's activities.

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Basically, adverse event report after vaccination is collected by free descriptive comments and sometime it is difficult to evaluate the reliability of diagnosis. Based on these actual situations, in abroad, standardized criteria was implemented for the collection and/or evaluation of spontaneous reports. In this article, we discussed regarding the measures to implement Brighton criteria, which is expanded as global standardized criteria, in Japan.

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Pharmacovigilance for vaccines has different considerations from other drugs. In this article, contributions of databases for vaccines pharmacovigilance are discussed, such as spontaneous case reporting databases and medical information databases (claims databases and electronic health record databases). Regarding spontaneous case reporting databases, some databases such as in-house databases and Japanese Adverse Drug Event Report database (JADER) have been already established, and can be utilized for detection of a vaccination failure, a vaccine quality defect-related issue and a statistical safety signal. In the future, a pharmacovigilance activity for vaccines with spontaneous case reporting databases will be expected to become more robust by integrating data which pharmaceutical companies and regulators respectively accumulate and by compiling data from current regulatory programs. Regarding medical information databases, while there is a critical limitation that vaccination information cannot be captured, some points can be utilized, for example, to understand background incidence/trend of events or infections. Also there is a possibility that an assessment by using medical information databases can be alternative means of current regulatory programs. In the future, a paradigm shift will be expected through establishment of further medical information databases, for example, by standardization of vaccine code on the electronic medical record and by linkage of vaccine data to the medical information databases.

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The reform of regulation is proposed to implement the Pharmacovigilance Planning (PVP) based on the ICH E2E guidelines as indicated in the notification of Risk Management Plan (J-RMP). Even after the J-RMP is enforced, the pharmacovigilance method still heavily depends on the traditional methods like “drug use results surveys”. The “Good Post-marketing Study Practice (GPSP)” ordinance and related notifications are the root causes of the malfunctioned operation of the system. Specifically, 1) the GPSP ordinance does not encourage the investigations according to the ICH E2E notification and 2) it is believed that the pharmacovigilance method should be limited to one of the three options only, namely, “drug use results surveys”, “specific use surveys” and “post-marketing clinical studies”. The followings are proposed:
• The GPSP ordinance should be revised to encourage referring the annex “pharmacovigilance methods” in “Pharmacovigilance planning”.
• The use of the early post-marketing phase vigilance (EPPV) should be restricted to the drugs marketed at the same time in the world or marketed for the first time in Japan.
• The notification connecting the “Good Vigilance Practice (GVP)” and GPSP ordinances (March 11, 2013, No 0311-7) should be revised to include a prescription that the “Safety Control Manager encourage the Post-marketing Surveillance Control Manager to develop a pharmacovigilance plan according to the ICH-E2E guidelines”.
• Forms attached to the individual RMP submissions should be revised according to the J-RMP notification.
• The notification on the RMP development (No.0426-1 and No.0426-2, on April 26, 2012) should be revised to indicate that the study design is acceptable to the health professionals.
• It should be clarified that the additional pharmacovigilance activities may be conducted by the divisional cooperation in the world or may be conducted as a non-clinical study, if appropriate.

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The concept of regulatory science (RS) was proposed in 1987 by Dr. Mitsuru Uchiyama. He describes “RS is the science of optimizing scientific and technological developments according to objectives geared toward human health. It is also the science of predictive evaluation. In properly carrying out the mission of regulation, we must engage in appropriate research activities and harmonize technology with society's needs. This can be accomplished only by accurately comprehending and carefully exploiting the characteristics and trends of new technologies, reactions, materials, and substances”. This article describes the development and the present status of RS in Japan, US and EU. FDA (US authority) defines RS as the science of developing new tools, standards and approaches to assess the safety, efficacy, quality and performance of FDA-regulated products, and considers RS as a useful tool to accelerate the approval of new drugs and their delivery to patients. On the other hand, PMDA (Japanese authority) takes RS as the norms of regulatory activities in assessment and approval of useful drugs to meet the needs of patients. Pharmacovigilance (PV), defined by WHO, is the pharmacological science relating to the collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products. PV focuses on safety of drugs and, therefore, can be a part of RS which deals with all aspects of pharmaceutical products including efficacy, safety and quality. The occurrence rate of adverse effects leading to death is revealed quite high by the studies in US and in Japan. Prediction and prevention of adverse effects are urgent matter that RS and PV should deal with.

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