Overview of Japan's Pharmaceutical Regulatory Framework

Japan has attracted much attention in Asia due to its highly mature pharmaceutical system and strict regulatory system. As the core agency for drug and medical device evaluation in Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) undertakes the important mission of ensuring the quality, safety and effectiveness of drugs. In this article, we will deeply discuss the responsibilities, review process, and post-marketing regulatory mechanism of PMDA, and then analyze the overall operation logic and characteristics of the Japanese drug regulatory system.

Functions of PMDA

PMDA is an independent administrative corporation directly under the Ministry of Health, Labour and Welfare (MHLW) and was established in 2004. The establishment of the agency aims to integrate the functions originally assumed by the drug review center, the medical device review agency and the safety monitoring agency, so as to achieve the integration of review and approval, the whole process of risk management, and the rapid response to emerging technologies.

PMDA is currently mainly responsible for the scientific review of drugs, medical devices and regenerative medical products, compliance inspections such as GMP/GCP, post-marketing safety monitoring (pharmacovigilance), and actively participates in international regulatory cooperation.

Drug Regulatory System in Japan

The drug regulatory system in Japan consists of three levels: the central competent authority MHLW, the technology assessment agency PMDA, and the local government regulatory agency.

• MHLW is responsible for making laws and regulations, approving new drugs to market, directing drug recalls and other major affairs.
• PMDA undertakes professional work such as review, compliance inspection and risk monitoring.
• Local governments are mainly responsible for drug retail management, daily implementation of GMP on-site inspection and other transoperational tasks.

In addition, Japan has integrated a variety of special laws and regulations to form a full-cycle drug regulatory legal system covering research and development, production, circulation, use and monitoring. PMDA plays the role of "technical core" in this system, providing scientific support for law enforcement, and guiding enterprises to carry out R&D and registration activities in accordance with Japanese regulatory requirements through institutional platforms.

PMDA-led Drug Evaluation Process

In the new-drug development cycle, PMDA has been involved from the early development stages. Typically, companies apply to PMDA for scientific advisory services when conducting pre-clinical studies or preparing for first-in-human trials. The consultation covers technical assessments of drug mechanisms of action, clinical trial design, statistical methods, and target population selection. This early intervention mechanism helps enterprises reduce the risk of clinical trial failure and improves the success rate of subsequent reviews.

An investigational new drug application (IND) is submitted to the PMDA after the initiation of the clinical study. The PMDA will review the adequacy of the non-clinical data and the ethical and scientific soundness of the trial design. During the trial, PMDA may perform GCP checks on the site to ensure the authenticity and reliability of the test data.

When the enterprise has completed the phase III clinical trial and accumulated sufficient safety and efficacy data, it can submit a New Drug Application (NDA) to the PMDA. The PMDA initiates a technical review process, which covers clinical data, CMC, statistical methods, safety summaries and risk control protocols. For drugs involving ethical controversy, social impact, or a complex risk-benefit ratio, the PMDA may submit the review materials to the expert committee of the "Pharmaceutical Affairs and Food Sanitation Council" for discussion, and thus form a final review opinion.

Fast-track Approval System

In general, the regular review period for new drugs is about 12 months. However, for drugs with strong innovation or urgent social needs, the PMDA has an accelerated review mechanism, which can shorten the review period to 6 to 9 months.

In order to encourage the R&D of innovative drugs and meet unmet clinical needs, the PMDA has established a variety of rapid review systems. Among them, the most representative systems include Priority Review, Sakigake Designation and conditional approval, which are mainly applied to rare disease drugs, regenerative medical products and new drugs with breakthrough mechanisms.

In addition, the PMDA has a conditional approval mechanism for regenerative medicine products. Conditional marketing is granted if clinical trials preliminarily confirm that the product has potential efficacy and the risks are manageable. After the product is marketed, the company needs to continue to carry out confirmatory clinical studies, and once efficacy is confirmed, it will be converted to formal approval. This "quick to market plus post-hoc validation" strategy accelerates the clinical application of emerging therapies and enables patients to benefit earlier.

Post-marketing Supervision

PMDA plays a key role in the regulation of drugs after marketing, and one of its core tasks is to establish and maintain a comprehensive pharmacovigilance system. All Marketing Authorization holders (MAH) must submit a post-marketing Risk Management Plan(RMP) to the PMDA, which covers potential risk identification, risk minimization measures and post-marketing research plans. PMDA evaluates RMP and makes the results publicly available to enhance regulatory transparency and public trust.

In terms of adverse events monitoring, PMDA has established a nationwide adverse event reporting network, with information sources including medical institutions, patients and enterprises. All serious adverse reactions need to be reported to PMDA within the specified time limit, and for major risk products, companies are also required to conduct special post-marketing investigations. The PMDA will aggregate adverse-reaction data into the JADER database and make it available to researchers and the public to facilitate the sharing and analysis of drug-safety information.

If major safety risks are found after marketing, PMDA can order the enterprise to modify the drug instructions, issue a Dear Healthcare Professional Letter, or even take compulsory measures such as product recall or withdrawal of license. Through this dynamic and hierarchical safety supervision mechanism, PMDA realizes risk control in the whole process from review to clinical use, and ensures public drug safety.

Proregulations conducts in-depth research on PMDA regulatory regulations and guidance documents, and specializes in assisting clients to adjust and optimize their product launch strategies in a timely manner to meet the challenges and opportunities in the Japanese market. If you are interested in our services or need more details, please contact us.