Evolution of the Japanese regulatory system and agencies

The Japanese regulatory system has been recognized as one of the most sophisticated and stringent regulatory systems in the world. The regulatory policies are developed and administered by the Ministry of Health, Labour and Welfare (MHLW), the Pharmaceuticals and Medical Devices Agency (PMDA) executes the policies, and certain authorities are delegated to local governments. Over the last 6 decades, the Japanese regulator has faced many challenges but has kept enhancing the system based on learnings from the challenges. PMDA has been very active in sharing regulatory knowledge with neighboring countries. This article traces the origin of the Japanese regulatory system and the significant events that have led to various enhancements to the laws and regulations in the last 6 decades. It also discusses the current regulatory system and the delegation of responsibilities between the agencies and their international collaborations.
 
Keywords – good manufacturing practice, MHLW, PMDA, PMD Act, quality management system, recognized certification body
 

Introduction

In Japan, it is necessary to comply with the regulations of Pharmaceutical and Medical Device Act (PMD Act)¹ at all times to manufacture, import, and sell drugs and medical devices. The MHLW² takes the central role in promulgating and administering regulations (henceforth referred to as “pharmaceutical affairs administration”) under the PMD Act. MHLW conducts operations and services related to pharmaceutical affairs administration while working with the PMDA and prefectural governments. The roles of each of these organizations are:
 

• MHLW develops and implements regulatory policies  and punitive actions for violations, such as approval and administrative orders related to healthcare products;
• PMDA conducts operations such as examinations, inspections, and data analysis before an administrative measure is implemented; and
• Prefectural governments have the authority to grant licenses as established under the PMD Act and related laws and to undertake pharmaceutical affairs administration in their jurisdictional prefectures.

 
The Japanese regulatory system has been recognized as one of the most sophisticated and stringent regulatory systems in the world, but its journey to achieving that status has not been smooth. Japanese regulators have faced many challenges in the last 6 decades but have kept enhancing the system with the learnings from the challenges. This article traces the origin of the Japanese regulatory system and significant events and enhancements in the last 6 decades and discusses the current regulatory system and overview of the government agencies.
 

Industry-led regulatory system: The Edo period (1603-1867)³

The first evidence verifying the existence of a Japanese pharmaceutical industry is in ancient documents recording that, in 1658, 33 “medicinal products retailers” in Doshomachi, Osaka, submitted joint seal letters describing a regulation dealing with “fake drugs.” Medicinal products retailers were the equivalent of today’s pharmaceutical corporations and were conducting business before the 1658 letters. In 1722, a special facility was established for the entire industry to monitor fake drugs and distribute good products to the market. This may be considered the beginning of drug good manufacturing practice (GMP) in Japan. In this way, the drug wholesale industry governed itself by actively offering its opinions in the form of joint seal letters from the companies to the Tokugawa Shogunate, the highest authority at that time. The methods used were not to regulate through laws or systems but to virtually eliminate defective products and unsuitable traders by sharing technologies and know-how among partners. It should be noted that a characteristically Japanese industry-led method was being used.
 
Another characteristic of the Edo period is that one could not become a large trader with a large network without obtaining a license to become a wholesaler. In other words, commercial transactions based on business licenses for drug wholesalers were being conducted during this period, and cartels of full-time traders were established.
 
There are many corporations that have been conducting business since the time of drug wholesalers, including today’s Takeda Pharmaceutical Co., Mitsubishi Tanabe Pharma Corp. (Tanabe Pharma Corp.) and Ono Pharmaceutical Co., as well as those that had developed from new branches or branch families, including Shionogi & Co and Astellas Pharma Inc. (Fujisawa Pharmaceutical Co.). The traditional pharmaceutical traders see the history of Doshomachi since the early Edo period as their own and still maintain its traditions and its pride.
 

Birth of quality assurance: End of the 17th century

Due to the development of Japan’s money economy at the end of the 17th century, the demand for drugs rapidly increased. Because trust in Japanese medicine was eroded by the distribution of counterfeits, the representatives of drug stores in Edo (the administrative capital of Tokugawa), Sumpu, Kyo, Osaka and Sakai were summoned for lectures in 1772, and the Six Points of Japanese Medicine, which are methods and standards of inspection of Japanese medicine, were established. At the same time, the special facilities mentioned previously were established in the five cities. The Six Points of Japanese Medicine can be said to be the basis for the later Japanese Pharmacopoeia, and we can see that quality assurance, one of the objectives of the Pharmaceutical Affairs Law,⁴ has been of serious interest since that time and substantially regulated.
 
It is important to mention that throughout the Edo period of more than 300 years, various arrangements regarding drug products were established, led by the industry, who offered proposals to the government, and to this day, the industry has maintained the position that there ought to be regulations.
 

Beginning of regulating manufacturing and marketing business: From the Meiji period (1868-1912)⁵

Because ports in Yokohama and Kobe were opened to trade in 1859 and 1867, respectively, medicine manufactured in foreign countries (Western medicine) started to be imported into Japan. With the Meiji Restoration in 1868, the period of the feudal Tokugawa government ended, and the period of the new Meiji government started. Under the new government’s lead, the wholesaler system and industries went through significant overhauling processes. Through such processes, the pharmaceutical industry that had existed since the Edo period was differentiated into the pharmaceutical and wholesale industries, creating the basis for the manufacturing and marketing businesses now regulated by the Pharmaceutical Affairs Law.
 

The Pharmaceutical Affairs Law in postwar Japan

In a country devastated by World War 2, the government and industries were in a state of chaos. Despite such chaos, the Enterprise Reorganization Act and the Pharmaceutical Affairs Law were newly promulgated in 1946 and 1948, respectively. However, pharmaceutical companies needed time to rebuild and transform into large, modern corporations in this immediate postwar period, and the government and pharmaceutical industry continued collaborating on refining the 1948 law until the Pharmaceutical Affairs Law of 1960 was enacted.
 
Since the enactment of the Pharmaceutical Affairs Law of 1960, the law has been revised numerous times to prevent recurrence of tragic health events, including deaths from penicillin shock, birth defects caused by thalidomide, and subacute myelo-optic neuropathy caused by chinoform agents. Technological advancements and changes in the society have also triggered major changes in how medical products are regulated. Following is a list of major amendments to Pharmaceutical Affairs Law and enactments and amendments to other major laws the in last 60 years.
 

Enactment of the current Pharmaceutical Affairs Law (1960)

• Established a system for quasi-drugs;
• For pharmacies, manufacturing, and sales businesses – Shifted from the registration system to a licensing system and established licensing standards;
• For sales businesses – Defined general sales medicinal product retailing, retailing by home distribution and special sales; 
• Established requirements for indications of lot numbers and quantity of ingredients;
• Limited advertisements of drug products for special diseases, such as cancer, and nonapproved drug products; and
• Separated matters associated with the identification of pharmacists (establishment of the Pharmacists Law).⁶

 

Fundamental Principles for Manufacturing Approval for Drug Products (1967)⁷

A major change in the character of examinations for approval in Japan was the Fundamental Principles Regarding Manufacturing Approval for Drug Products, issued in 1967. This document addressed:
 

• Classification of professional use drugs and over-the-counter (OTC) drugs;
• Prohibition of advertisements for professional use drugs targeting the general public;
• Standardization and tightening of review policy; and
• Mandatory reporting of side effects for at least 2 years after obtaining a new drug approval.

 
These principles clarified what information was required in the drug submission and categorized and examined professional-use and OTC drugs. Moreover, the reporting of information on side effects for 2 years after obtaining approval became mandatory, contributing to the establishment of a regulatory system for medical devices. However, because it was a time when neither good clinical practice nor good laboratory practice existed, it was mandatory to publish information at academic conferences or in academic journals to ensure the data integrity. This requirement continued until the fundamental principles were revised in 1999.
 

Enactment of the Adverse Drug Reaction Sufferings Relief Fund Law (1979)⁸

The Adverse Drug Reaction Sufferings Relief Fund Law was enacted in 1979 and the Adverse Drug Reaction Sufferings Relief Fund established the same year. The law required the provision of necessary benefits to relieve sufferers from adverse drug reactions and stipulated manufacturers had to bear the costs and establish the fund.
 
The law was an outgrowth of discussions at a 1973 conference about setting up a relief system for patients who suffered adverse drug reactions and a subsequent 1977 outline of the relief system.
 

Amendment of the Pharmaceutical Affairs Law (1979)

This marked the first major reform since the enactment of the law in 1960. The amended law:

• Established regulations regarding approval, such as making products listed on the Japanese Pharmacopeia subject to approval;
• Established regulations for reexamination systems for safety assurance after approval of new drugs;
• Established regulations for drug reevaluation systems to review efficacy and safety based on developments in science and technology;
• Required mandatory labeling of the expiration date of drug products and the ingredients of cosmetics;
• Required mandatory provision of information from manufacturers to distributors; and
• Required mandatory notification of clinical trial plans.

 

Amendment of the Pharmaceutical Affairs Law (1993)

• Mandatory provision of information from manufacturers to distributors;
• Regarding intended use, the phrase “taking necessary measures to promote research and development for drug products and medical devices with especially high demand for medical usage” was added to the objectives of the law;
• Systems, including subsidies for priority inspections, tax breaks, and experiments and research were introduced for drug products recognized as being in high demand for medical usage, including those for rare disorders;
• Following specific requirements for drug products, including those for rare disorders, the following were added;
  • The number of target patients should be 50,000 or fewer;
  • Products must have exceptional value related to their intended use; and
  • Drug development must be feasible.

 

Amendment of the Pharmaceutical Affairs Law (1994)

• Designated cardiac pacemakers, and other devices, as “specially designated medical device[s]” and mandated record preparation and retention for a certain period;
• Introduced reexamination and reevaluation systems for medical devices;
• Consigned some evaluation operations for medical devices to a designated corporation (Japanese Association for the Advancement of Medical Equipment, or JAAME); and
• Added GMP to the approval requirements for manufacturing medical devices.

 

Amendment of the Pharmaceutical Affairs Law (1996)

The amendments addressed:

• Mandatory reporting of the side effects of investigational drugs;
• Data integrity assurance for applications for approval, reexamination, and reevaluation;
• Mandatory reporting of side effects and infectious diseases;
• Reporting of recalls;
• Improved provision of information by distributors and pharmacists; and
• Introduction of special approval system.

 

Amendments of the Pharmaceutical Affairs Law and Blood Donation and Collection Service Control Law (2002)⁹

• Pharmaceutical Affairs Law –  Introduction of marketing authorization holder system, risk-based classification of medical devices and introduction of review system of third-party certification bodies; and complete reform of safety policy regarding medical devices.
• Blood donation law –  Reinforcement of safety assurance policies for biological products and reinforcement of postmarket safety policies and revision of approval and license systems.

 

Amendment of the Pharmaceutical Affairs Law (2006)

Due to the rapid increase of aging population, the increase in lifestyle-related diseases, and the increase in self-medication, OTC drugs have been classified into categories 1 to 3 according to their risks. Import, manufacture, sale, provision, storage for sale of designated drugs have already been prohibited, but possession, use, purchase, and transfer were newly prohibited. The amendments addressed:
 

• Revision of drug sales regulations – OTC drugs were classified into classes 1-3 risk categories, with sales methods, distinguished for each category;
• Matters related to registered seller system – Establishment of a new specialist system separate from pharmacists, who are responsible for selling OTC drugs’ and
• Prohibition of possession and use of designated drugs (designated drug was defined as a substance with a high probability of being psychotoxic).
   

Enactment and amendment of the Pharmaceutical and Medical Device Act (2013 and 2019)
The Pharmaceutical Affairs Law of 1960, last amended in 2006, was revised to strengthen safety measures related to pharmaceuticals and medical devices; establish regulations based on the characteristics of medical devices; and establish regulations based on the characteristics of products, such as regenerative medicine. Under the regulatory reform in 2013, a dedicated chapter for medical devices was created. Subsequently, the regulatory reform in 2019 added some elements to the regulatory system to take advantage of increasingly digitized society and digital technology. Those elements include:
 
Enactment (2013)

• Strengthening safety measures for pharmaceuticals and medical devices:

• Clearly stated that the prevention of the occurrence and spread of health hazards is one of the purposes of the law; and
• Prepare a package insert based on the latest scientific findings and notify the Minister of Health, Labor and Welfare.

 

• Generating regulations based on the characteristics of medical devices and in vitro diagnostic reagents:

• Since the characteristics of pharmaceuticals, quasi-drugs, and cosmetics are different from those of medical devices, regulations regarding the manufacturing licenses and marketing authorization licenses for medical devices are set up as a new chapter based on the characteristics;
• Changed the permit/certification system for the manufacturing industry to the registration system;
• Revised the Quality Management System (QMS) Ministry Ordinance to streamline the investigation method;
• Transferred some examinations of highly controlled medical devices (Class II) to a certified review body; and
• Included regulation of software as a medical device.

 

• Regulations based on the characteristics of products, such as regenerative medicine:

• In addition to the existing drugs, quasi-drugs, cosmetics, medical devices and designated drugs, a new "product such as regenerative medicine" was added and defined.
• Introduced a system to approve nonhomogeneous regenerative medicine products at an early stage with conditions and time limits by estimating efficacy and confirming safety.

 

• Change of the name of the law (Pharmaceutical Affairs Law)

• Based on these contents, the name of the Pharmaceutical Affairs Law was changed to "Law Concerning Quality, Effectiveness and Safety of Pharmaceuticals, Medical Devices, etc."

 
Amendment (2019)
The Pharmaceutical and Medical Device Act was amended in 2019, and the following changes occurred regarding medical devices:

• Digitization of information (instructions for use) such as precautions and posting on the PMDA homepage (enforced in September 2021);
• Establishment of legal compliance system for marketing authorization holders and manufacturers (enforced in September 2021); and
• Compliance with unique device identifier requirements (will be enforced in December 2022).

 

Current organizational structure of agencies

As discussed in previous section, there have been many changes in the laws and regulations that regulate drugs and medical devices. To effectively implements those changes, the regulatory agencies also have gone through many changes. This section discusses the way in which agencies are set up and interact and the delegation of certain roles in their pharmaceutical affairs administration.


Ministry of Health, Labour and Welfare
MHLW is one of the central government ministries under the Cabinet that runs the government. It is an administrative institution that was inaugurated when the former Ministry of Health and Welfare and the Ministry of Labour were integrated as part of the restructuring of the central government on 6 January 2001.
 
MHLW’s duties for securing and improving the lives of citizens include the provision of aid to repatriates and war victims and survivors, as well as families and relatives of nonrepatriated persons; the improvement and enhancement of social welfare, social security, and public health; the improvement of the working environment for laborers; and the securing of employment.
 
MHLW is composed of the headquarters and external bureaus. Internal offices (Minister’s Secretariat, 11 bureaus and the Director-General for Policy Planning), affiliated institutions, councils (e.g., the Pharmaceutical Affairs and Food Sanitation Council) and regional bureaus acting as field agencies that handle different matters (Regional Bureaus of Health and Welfare and Prefectural Labour Bureaus) are based in the headquarters. The external bureaus consist of the Social Insurance Agency and the Central Labour Relations Commission.
 
Within MHLW, pharmaceutical affairs administration is managed primarily by the Health Policy Bureau, the Pharmaceutical and Food Safety Bureau (PFSB) and the Pharmaceutical Affairs and Food Sanitation Council. Of these bureaus, PFSB grants licenses and enforces regulations for clinical trials, evaluations and postmarket safety measures. The majority of those tasks are delegated to the PMDA, but MHLW is the ultimate decision maker.
 
Pharmaceuticals and Medical Devices Agency¹⁰
PMDA is an organization established under the Pharmaceuticals and Medical Devices Agency, or PMDA, Law based on the Reorganization and Rationalization Plan for Special Public Corporations¹¹ approved by the Cabinet in December 2001. It integrates some of the affairs of the Organization for Pharmaceutical Safety and Research (OPSR), the National Institute of Health Sciences, and JAAME, and was established in April 2004.
 
PMDA’s objectives are to provide prompt relief for health damages caused by adverse reactions to drug products or infections via biological products, and to conduct investigations that help to improve drug product quality, effectiveness and safety, thus contributing to the improvement of national health (Article 3 of the PMDA Law). The agency’s major areas of focus can be categorized broadly into three parts: health damage relief affairs, product review affairs, and safety policy affairs.
 
For product reviews, PMDA cooperates mainly with PFSB of MHLW and conducts operations such as evaluations, investigations, and data analysis for the stages from preclinical trials to postmarket surveillance. Previously, reviews of drug products were conducted by the National Institute of Health Sciences, and consulting affairs regarding clinical trial plans were conducted by the OPSR, but with the establishment of PMDA in 2004, a consistent guidance and evaluation system covering the stages from preclinical trials to approval and postmarket was created. In addition, the affairs of the Research and Development Division were transferred to the National Institute of Biomedical Innovation established on 1 April 2005.
 
The PMDA organization consists of 28 departments and 4 groups. Originally all functions were located in Tokyo, but the Kansai branch and the Hokuriku branch were later established to extend their operations to provide the services to those western parts of Japan where the pharmaceutical and medical device industries are located.
 
Key focuses of PMDA. As shown in the accompanying Figure, the PMDA focuses on review, safety, and relief operations.
 

 
Key activities of PMDA. The agency’s key activities within each focus area include:
 

• Review
  • Premarket reviews for products such as pharmaceuticals, medical devices, and regenerative medicine;
  • Re-examinations/re-evaluations;
  • Data integrity review for premarket submissions;
  • GMP/QMS/GCTP (good gene, cellular, and tissue-based products manufacturing practice) inspections for manufacturing plants;
  • Supervision on registered certification bodies; and
  • Standard development the Japanese Pharmacopoeia.

 

• Safety
  • Reception work for notification of package inserts;
  • Collecting and organizing information on side effects from manufacturers or medical institutions;
  • Research and analysis work that contributes to safety measures through scientific analysis;
  • Consultation services regarding safety measures from manufacturers;
  • Responding to consultations from the general public; and
  • Information service related to the safety of pharmaceuticals, medical devices, regenerative medicine products, and so on.

 

• Relief

• Relief system for sufferers from adverse drug reactions;
• Relief system for sufferers from infections via biological products;
• Consignment and loan affairs;
• Including healthcare allowances for patients with subacute myelo-optic neuropathy;
• Commissioned benefits affairs, including benefits such as healthcare allowances for HIV-positive and AIDS patients
• Payment of benefits based on the law on special measures concerning the payment of benefits to relieve victims of hepatitis C infected through specific concentrates and specified coagulation factor XI concentrates.

 
These relief systems are funded by the annual contributions from industry.
 
PMDA organizational structure. The agency consists of 22 offices and 1 section, overseen by a chief actuary. An outline of the major activities of each department conducting affairs related to product reviews and safety measures is shown below.

• The Office of Review Administration coordinates product reviews and conducts affairs related to the appointment of specialist discussion committees.
• The Office of Review Management primarily conducts planning and development of review operations and audits. It conducts a variety of operations, including, those related to: collection or management of information regarding operations for examinations; process management; process adjustments for face-to-face consultation regarding new drug products in each review administration office; arranging face-to-face consultations; and communication management with each review administration office.

 
The following is a list of product-specific offices:

• Office of New Drugs I ‒ digestive system drugs, drug for external use, immunosuppressive agents, hormonal agents, and drugs for metabolic diseases.
• Office of New Drugs II ‒ cardiovascular agents, anti-Parkinson’s disease drugs, drugs for improving cerebral circulation and metabolism, drugs for Alzheimer’s disease, drugs for genitourinary and anal use, compound agents for medical use, radioactive agents, contrast agents.
• Office of New Drugs III ‒ central nervous system drugs, peripheral nervous system drugs, drugs for sensory organs (except those related to inflammatory diseases) .
• Office of New Drugs IV ‒ anti-infective drugs, drugs for sensory organs (except those related to inflammatory diseases), drugs for respiratory organs, allergy.
• Office of New Drugs V ‒ anticancer drugs.
• Office of Biologics I ‒ blood coagulation factor products, drug products and medical devices for gene treatment, antibody products, and products subject to the Cartagena Law .
• Office of Biologics II ‒ vaccines, antitoxins and drug products for cell treatment, drug products and medical devices using cell tissue.
• Office of OTC/Generic Drugs ‒ generic drugs, OTC drugs, quasi-drugs and cosmetics, as well as investigations to confirm export certifications and confirm quality reassessments.
• Office of Medical Devices I and II ‒ these offices conduct necessary reviews for the approval of medical devices and in vitro diagnostics, necessary confirmation for reexamination and reassessment, investigations regarding clinical trial plans and investigations for face-to-face consultation and discrepancy reports during clinical trials.
• Office of Software as a Medical Device
• Office of In Vitro Diagnostics

 
The following offices carries out safety and compliance related operations for drugs or medical devices:

• Office of Standards and Compliance for Medical
• Office of Manufacturing Quality and Vigilance for Medical
• Office of Manufacturing Quality for Drugs
• Office of Informatics and Management for Safety
• Office of Pharmacovigilance I and II

 
Delegation of tasks between MHLW, PMDA, and prefectural governments
From among the administrative duties under the authority of the Minister of Health, Labour and Welfare as stipulated in the PMD Act, some related to the authority to grant approval for manufacturing and marketing, as well as all those related to the authority to provide licenses, are consigned to the prefectural governments.
 
The division of tasks between the MHLW/PMDA and the prefectural governments for the major procedures regarding the marketing authorization of drug products and medical devices are shown in Table 1. For obtaining a marketing authorization, a successful premarket inspection is a key. Depending on the product seeking a marketing authorization and where the manufacturing facility is located, inspecting governmental organization varies, as shown in Table 2.
 

 

 

International activities

The PMDA has been putting significant emphasis on becoming a leading regulatory agency in Asia by sharing best practices established for drugs and medical devices in the Japanese market. Following is the excerpt of PMDA International Strategic Plan 2015:¹²
 
Pharmaceuticals and Medical Devices Agency (PMDA) has succeeded in shortening the review period for medical products to the world’s top standard through its 1st and 2nd Mid-term Plan Periods (FY 2004 to 2013). PMDA has been highly evaluated internationally for this and other achievements, and now positioned to contribute more to the world. In order to respond to the domestic and global expectations, PMDA has developed and announced its strategic plan titled “PMDA International Strategic Plan 2015”.
 
This Strategic Plan outlines the international activities that will be conducted in the period defined in the 3rd and 4th Mid-term Plans, ending in FY 2023, taking into consideration the changes in the regulatory environment, as well as the Regulatory Strategy Initiative set forth by the Ministry of Health, Labour and Welfare (MHLW) in June 2015. As the development, manufacture, and distribution of pharmaceuticals, medical devices, and cellular and tissue-based products are becoming increasingly globalized, PMDA must collaborate with foreign regulatory authorities and other related parties. PMDA will make strenuous efforts in its international activities along with conducting efficient and effective product reviews, implementing safety measures, and providing relief services. Below are the key international actions set forth in the “PMDA International Strategic Plan 2015”.
 

• Establish the “Regulatory Science Center” for conducting first-in-the-world product reviews, implementing safety measures, and undertaking other activities, as well as publishing the outcomes.
• Launch the “Asian Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs” to share PMDA’s accumulated knowledge and experience in product reviews, implementation of safety measures, and provision of relief services with Asian and overseas regulatory authorities.
• Cooperate with overseas regulatory authorities for expansion of harmonization activities (e.g., ICH, IMDRF [International Medical Device Regulators Forum])and work- sharing (e.g., GMP/QMS inspections)
   

Establishment of the PMDA’s Asia Training Center

By following the PMDA International Strategy of 2015, Asia Training Center (ATC) for Pharmaceuticals and Medical Devices Regulatory Affairs,¹³ or PMDA-ATC, was established in April 2016 to actively share the knowledge and experience obtained in Japan with regulatory authorities in Asian countries. The PMDA Hokuriku branch, which was established in June of the same year, provided training on GMP inspections. Through these trainings, PMDA is aiming at elevating regulatory competency and harmonization in Asia, and further strengthening the cooperation system within the region and beyond.
 
PMDA-ATC has been certified by the Asia-Pacific Economic Co-operation as a center of excellence in three areas: international clinical trial/good clinical practice inspection; drug safety monitoring; and medical device area. In addition, the joint declaration of the 2017 meeting of health ministers from Japan and the Association of Southeast Asian Nations (ASEAN) ¹⁴ stipulates use of PMDA-ATC to improve the capacity of ASEAN countries' authorities.
 

Promoting regulatory science

Work at a regulatory agency requires incorporating the latest scientific knowledge and making accurate predictions, evaluations, and judgments based on clearer evidence. To improve the quality of these operations, PMDA has promoted regulatory science, and the Regulatory Science Center¹⁵ was established in April 2018.
 
Research support and promotion work, next-generation evaluation methods, promotion work, medical information utilization work, and so on, are carried out collaboratively at the center, mainly by the premarket review department and the safety department to improve the quality of premarket reviews and postmarket safety measures.
 

Conclusions

Japan’s regulatory scheme was originated from a bottom-up approach by industry’s leadership and collaboration with the government to prevent distribution of fake drugs. Whereas regulatory schemes in other countries have taken a top-down approach with government leadership, Japan’s approach looks very unique in this point. Over the decades Japan had gone through many challenges, such as wars and numerous health hazard events, but it continued strengthening its regulatory system to prevent recurrence.
 
Expansion of the global economy and rapidly advancing medical technologies necessitated the Japanese regulator to transform its organization and operations to accommodate advanced medical technologies that have much shorter life cycle than pharmaceutical products. Establishing the medical device unit within the PMDA, is a good example of the organizational transformation to realize more efficient total product life cycle management.
 
In recent years, the PMDA has been very active in expanding their activities toward Asia in sharing their experience and knowledge to support regulatory capacity building in the region. The PMDA-ATC would serve as a core of such activities and contribute to regulatory capacity in the region. In addition to the activities in Asia, Japan also serves as a member of IMDRF Management Committee. I hope that Japan would become a driving force for regulatory convergence, ultimately realizing a medical device single review program.
 
Acronyms and abbreviations
ASEAN, Association of Southeast Asian Nations; ATC, Asia Training Center [for Pharmaceuticals and Medical Devices Regulatory Affairs]; GMP, good manufacturing practice; IMDRF, International Medical Device Regulators Forum; MHLW, Ministry of Health, Labour, and Welfare; OTC, over-the-counter; PMD [Act], Pharmaceutical and Medical Device [Act]; PMDA, Pharmaceuticals and Medical Devices Agency; QMS, quality management system; SMON, subacute myelo-optic neuropathy.
 
About the author
Susumu Nozawa, RAC, FRAPS, is head of regulatory policy for North America at Siemens Healthineers in Malvern, PA. He is responsible for proactively monitoring relevant technical regulations and standards to identify critical regulatory policy changes and opportunities and to communicate with and coordinate all stakeholders to realize favorable regulatory/business environment for Siemens Healthineers, industry, and the patients. He has more than 30 years of experience in the medical device industry and has held various positions in research and development, regulatory affairs and compliance, and quality assurance for global operations. Nozawa currently serves as a vice chair of the standards committee at the Medical Imaging Technology Alliance and actively participates in working groups and technical committees at various standards-developing organizations and trade associations. He is a mechanical engineer by training and holds the Regulatory Affairs Certification (US and EU) and is a RAPS Fellow. He can be reached at susumu.nozawa@siemens-healthineers.com
 
Citation Nozawa S. Evolution of Japanese regulatory system and agencies. RF Quarterly. 2022;2(2):4-16. Published online 27 June 2022. https://bit.ly/3nlcwet

 

References

All references accessed and/or verified 17 June 2022.
 
Prime source for the information in this article is from Fundamentals of Japanese Regulatory Affairs, First Edition. Edited by Nozawa S, Adachi H, Shouji K. RAPS; 2010.

1. [In Japanese] Pharmaceutical and Medical Device Act. e-gov website. https://elaws.e-gov.go.jp/document?lawid=335AC0000000145
2. Ministry of Health, Labour and Welfare website. https://www.mhlw.go.jp/english/
3. Britannia. Tokugawa period. https://www.britannica.com/event/Tokugawa-period
4. [In Japanese] Pharmaceutical Affairs Law. e-gov website. Amended 1 August 2021. https://elaws.e-gov.go.jp/document?lawid=335AC0000000145_20210801_501AC0000000063
5. Britannia. Meiji restoration. https://www.britannica.com/event/Meiji-Restoration
6. [In Japanese] e-gov website. Pharmacists Law. https://elaws.e-gov.go.jp/document?lawid=335AC0000000146_20200901_501AC0000000063&keyword=%E8%96%AC%E5%89%A4%E5%B8%AB%E6%B3%95
7. [In Japanese] Principles for Manufacturing Approval for Drug Products. MHLW website. Issued 1967. https://www.mhlw.go.jp/shingi/2009/01/dl/s0115-3b_0004.pdf
8. [In Japanese] Adverse Drug Reaction Sufferings Relief Fund Law of 1979. https://www.shugiin.go.jp/internet/itdb_housei.nsf/html/houritsu/08819791001055.htm#:~:text=%E6%B3%95%E5%BE%8B%E7%AC%AC%E4%BA%94%E5%8D%81%E4%BA%94,%E5%9B%9B%E3%83%BB%E4%B8%80%E3%80%87%E3%83%BB%E4%B8%80%EF%BC%89&text=%E7%AC%AC%E4%B8%80%E6%9D%A1%20%E5%8C%B
9. [In Japanese] Blood Donation and Collection Service Control Law of 2002. https://www.shugiin.go.jp/internet/itdb_housei.nsf/html/housei/15420020731096.htm
10. 9Pharmaceuticals and Medical Devices Agency website. https://www.pmda.go.jp/english/index.html
11. Reorganization and Rationalization Plan for Special Public Corporations. Dated 19 December 2002. https://japan.kantei.go.jp/policy/gyokaku/kettei/021219tokusyu_e.html
12. PMDA International Strategic Plan 2015. Dated June 2015. https://www.pmda.go.jp/english/int-activities/outline/0017.html
13. PMDA Asia Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs. https://www.pmda.go.jp/english/int-activities/training-center/0001.html
14. Association of Southeast Asian Nations website. https://asean.org/
15. PMDA Regulatory Science Center. https://www.pmda.go.jp/english/rs-sb-std/rs/0003.html