Nobumasa Nakashima
Pharmaceuticals and Medical Devices Agency (PMDA)

or the last 15 years, PMDA has taken several steps to deliver safer and more effective medicines and medical devices to patients. PMDA has drastically shortened its review times, which has resulted in a substantial decrease of the so-called “drug lag.” Recently, PMDA established the Asian Training Centre (ATC) for Pharmaceuticals and Medical Devices Regulatory Affairs and the Center for Regulatory Science.

In April 2019, PMDA welcomed its new chief executive, Yasuhiro Fujiwara, who has established four new priority areas (the “4 Firsts”). In addition, the Pharmaceuticals and Medical Devices (PMD) Act, the fundamental statute for pharmaceuticals and medical devices regulation in Japan, is under revision and deliberation in the Diet (the Japanese Parliament).

The PMDA Town Hall at the Global Annual Meeting provided regulatory updates as well as an overview of Fujiwara’s new priority areas and the revision of Japan’s Pharmaceutical and Medical Device (PMD) Act.

Key Takeaways

• Yasuhiro Fujiwara, the new Chief Executive of PMDA, established four new priority areas (the “4 Firsts”): 1. Patient First, 2. Access First, 3. Safety First, and 4. Asia First.
• The revision of the PMD Act is under discussion in the Diet and includes legislation for the “SAKIGAKE designation system” and the “Conditional early approval system.”
• ATC has provided a series of training seminars to foreign regulators to build mutual confidence among regulators and learn ICH and IMDRF guidelines. In fiscal year 2018, ATC hosted ten training seminars for 267 regulators from 31 countries or regions.
• PMDA has also established the Center for Regulatory Science aimed at strengthening reviews and consultations as well as safety measures by promoting regulatory science and human resource development.

The Future of PMDA – The “4 Firsts”

The four new priority areas proposed by Fujiwara align with and have evolved from his predecessor Tatsuya Kondo’s Rational Medicine Initiative and regulatory science policy.

1. “Patient First” is about communicating well with healthcare professionals and giving the highest priority to patient satisfaction. In May 2019, PMDA established a Patient Centricity Working Group, which is going to discuss how patients can be involved in PMDA’s review and safety activities. Guidance and principles will be developed to promote patient engagement.
2. “Access First” is about accelerating access to innovative medical products that are in public demand, while ensuring an appropriate risk-benefit balance. Key regulatory actions towards “Access First” includes the SAKIGAKE Designation System, the Conditional Early Approval System, Real World Data Utilization and International Collaboration.
3. “Safety First” is about implementing efficient post-marketing data collection and product distribution control, especially for a product subject to the accelerated approval scheme. The Conditional and Time-limited Approval System for regenerative medical products was launched to continuously manage a product’s safety after conditional approval. In addition, PMDA has Relief Services for adverse health effects; this program provides compensation for health damages associated with appropriate use of the product. This ensures that patients can use the product with a sense of assurance. Furthermore, the PMDA-qualified medical information database (MID-NET) came into full operation in April 2018. Besides PMDA using MID-NET for pharmaco-epidemiological studies, this database can also be used by pharmaceutical companies for their post-marketing studies.

4. “Asia First” is about promoting regulatory harmonization and improving public health across Asian countries or regions. The Asian region shares similarities in geography, genetics, and culture. This means that products can be developed more efficiently, leading to early access in this region. One unique initiative offered by PMDA is the ATC.

Proposed Revision of the PMD Act (Legislative Process Pending)

The PMD Act is the law for pharmaceuticals and medical devices statute in Japan and is now under review after a five-year implementation of the current law. This revision is to create a regulatory foundation for securing the future public health in Japan. The goal of the revision is to improve regulatory systems including safety measures, to provide medicines and medical devices to patients in a timely manner, while considering technology innovations and globalization. There are three main themes in the revision: 1. modernization of the regulatory system, 2. value of community pharmacies/pharmacists, and 3. prevention of illegal activities.

Proposed measures for the modernization of the regulatory system include legislation of the following approval schemes:

• SAKIGAKE Designation System – This system is applicable to innovative medicines, medical devices, or regenerative medical products in practical use in Japan sooner than or simultaneously with other countries, aiming at early practical application with various supports such as “Rolling Review,” “Priority Consultation,” and “Priority Review.”
• Conditional Early Approval – To accelerate patient access to drugs that treat serious diseases with particularly high medical needs and limited treatment options, as well as difficult-to-conduct confirmatory clinical trials (due to, e.g., the small number of patients or long trial periods). Conditions such as post-marketing studies to confirm efficacy and safety shall be set at the time of approval in addition to a certain level of efficacy and safety demonstrated in exploratory clinical studies.