Japan Reach Regulation for Various Sectors

The Reorganization and Rationalization Plan for Special Public Corporations that was approved in a Cabinet meeting in 2001, was followed by the establishment of the Pharmaceuticals and Medical Devices Agency (PMDA) and came into service on April 1, 2004, under the Law for the Pharmaceuticals and Medical Devices Agency, as a consolidation of the services of the Pharmaceuticals and Medical Devices Evaluation Center of the National Institute of Health Sciences (PMDEC), the Organization for Pharmaceutical Safety and Research (OPSR/KIKO), and part of the Japan Association for the Advancement of Medical Equipment (JAAME). The Pharmaceuticals and Medical Devices Agency (PMDA) is Japan's regulatory authority. It is subordinate to the Ministry of Health, Labour and Welfare (MHLW). The mission of the MHLW is to protect the population of Japan against health hazards caused by pharmaceutical products and medical devices that are not sufficiently safe or effective or not of sufficiently high quality 

With regard to the regulation of medical devices, the MHLW's tasks include: 

• Registering manufacturers 

• Licensing certain actors (MAH, dealers and repair service providers) 

• Enacting ministerial ordinances, guidelines and industry standards 

• The final release of medical device authorizations 

• Monitoring the PMDA 

The PMDA, which was created in 2004, is responsible for the actual tasks within the authorization procedures for medicinal products, medical devices and regenerative medicine products for the Japanese market. The PMDA’s most important tasks include: 

• Conducting the authorization procedures, including the regulatory review 

• Providing advice on clinical studies and authorizations being targeted 

• Inspections of manufacturers for compliance with Good Manufacturing Practices (GMP) 

• Market surveillance. 

Step 1: Establish a QM system 

As a foreign manufacturer, you do not have to demonstrate “home country approval” to have a medical device authorized in Japan. However, an ISO-13485 certificate will help you a lot when it comes to demonstrating that the Japanese quality management (J-QMS) requirements have been met.

Step 2: Establish the necessary roles 

Marketing Authorization Holder (MAH) 

As the next step, as the manufacturer, you have to appoint a local authorized representative, known as the Marketing Authorization Holder (MAH). The MAH assumes liability for your devices in Japan and is the owner of the authorization. Not every citizen is allowed to be an MAH. The MAH must first apply for a license (business license known as KYOKA) from the MHLW.

Step 3: Register as a manufacturer 

Before having your medical device authorized in Japan, you must, with the help of the marketing authorization holder (MAH), register as a foreign manufacturer with the Ministry of Health, Labour and Welfare (MHLW). All manufacturing sites responsible for development and final assembly or production must be registered. Component manufacturers do not have to register. 

• Information on the person responsible for regulatory compliance 

• Information on the production site

Step 4: Classify the medical device 

The PMD Act differentiates between three types of medical device: general, controlled and specially-controlled medical devices. These are divided into four classes: I (low risk), II, III, IV (high risk).

Medical device companies interested in offering their products in Japan must comply with Japan's Pharmaceuticals and Medical Devices Act (PMD Act). Complying with the PMD Act can be challenging for foreign manufacturers, as very few regulatory documents are published in English. As part of the approval process, medical device manufacturers must: 

• Comply with MHLW Ordinance No. 169 related to quality management systems 

• Appoint an in-country representative (MAH/D-MAH) 

• Register design and manufacturing facilities, among other requirements 

• Identification of compliance requirements under various guidelines including all data requirements.​ 

• Data gap analysis and pre-assessment support​ 

• Technical documentation support​ 

• Pre and post submission support and technical liaison with authorities.

The Cosmetic Act is issued by the Pharmaceutical and Medical Devices Agency (PMDA) of Japan, and it is supported by a series of subsidiary rules, standards and guidance documents issued by the competent authority, Ministry of Health, Labour and Welfare (MHLW). The main regulations concerning cosmetics in Japan are  “Pharmaceutical and Medical Device Law”(issued 14/09/2019)  and “Standards for Cosmetics”(issued 01/04/2001)

There are more than 10 Existing Key Cosmetic Regulations in force, for example, “Act for Ensuring Quality, Effectiveness, and Safety of Pharmaceutical and Medical Devices”, which came into force on September 14^th, 2019.

According to Article 2.3 of the Pharmaceutical Affairs Law, “cosmetics” is defined as articles with mild action on the human body which are intended to be applied to the human body through rubbing, sprinkling or other similar methods, aiming to clean, beautify and increase the attractiveness, alter the appearance or to keep the skin or hair in good condition.

Cosmetic products include two main categories in Japan.

1. Cosmetics: products that aim to maintain beauty, which can enter the market without notification nor registration.
2. Quasi-drugs: products that contain an active ingredient with a weak but real pharmacological activity on the human body (while not falling into the category of drugs) and aim at prevention and modification, which need approvement by authorities to enter the market.

The common quasi-drugs product types in Japan include the following:

• Anti-dandruff
• Whitening
• Anti-acne
• Anti-bacterial
• Anti-chapping
• Against drought
• Medicated soaps
• Haircare
• Deodorant
• Antiperspirant
• Product for hair regrowth
• Hair dyes
• Perm products
• Toothpaste
• Bath salts
• Products for breath
• Oral care

Ingredients:

1. Actives: the registration is easier for recognized actives that are already listed, but it is also possible to use new active(s)
2. Excipients: limited to the positive ingredient list (around 8000 substances), but also possible to use new excipient(s)

A thorough documentation of the active ingredient should be provided to the Pharmacy agency: Pre-Marketing Registration and Approval (PMDA). The agency will fully verify the product and claimed effects and then a specific labelling with the term "quasi drug" will be provided. A monograph is possible to follow for certain products.

The ingredients

"The ingredients of cosmetic products, including the impurities they contain, must not contain anything that could cause infection or make the use of cosmetic products hazardous to health” --Standard for Cosmetics

To help the manufacturers with their formulation, the Cosmetic Act has establish the following documents :

• Prohibited substances list, it is annexed to the Standard for Cosmetics. It gathers 30 prohibited substances, the Class I and II lists of the Chemical Substances Control Law (CSCL) and the substances from the Poisonous and Deleterious Substances Control Act.
• A restricted substances list
• An authorized preservatives list
• A positive list of the UV filters

The Label and claims

The labelling should be in Japanese and present the following :

• Name and Address of Marketing License Holder
• Product name
• Batch number
• Net weight
• List of ingredients (Japanese INCI)
• The expiry date for cosmetics specified by the MHLW announcement
• Precautions for use, instructions for use
• Country of origin

"Codes on Fair Competition regarding the representations of cosmetics" are Volontary standards on labelling and claims which are widely observed in Japan.

A list of 56 accepted efficacy claims for cosmetics is establish to prevent companies from giving unreasonable premiums and misleading representations claims. The Cosmetic Act :

• Ban wrong, misleading or exaggerated statements
• Prohibit assigning unprovable properties to the product
• Inhibit claims related to quasi-drugs or drugs for cosmetics

Nanotechnology in Japan has been controlled under existing regulatory frameworks for the safe management of tiny particles, such as the Roudou Anzen Eisei Ho (the Industrial Safety and Health Act) and the Haikibutsu Shori Ho (the Chemical Substances Control Act). While there is no nanotechnology-specific law, the Ministries of Economy, Trade, and Industry (2009) and Health, Labor, and Welfare (2008a) have been actively interested in researching nanomaterial safety measures. Engineered nanomaterials represent exceptional safety hazards due to their potential toxicity to people, particularly when breathed, and their ability to stay in the environment and accumulate in biological tissues.

The Ministry of Health, Labor, and Welfare (2008b) published a tsuuchi (notice) on occupational safety measures to avoid nanomaterials exposure during production and treatment. A year later, a group of Japanese experts from industry and academia, the Independent Study Group on Environmental Impacts of Nanomaterials (2009), produced a "Guideline for the Prevention of Environmental Impact with Regard to Industrial Nanomaterials." It's worth noting that Japan's regulatory emphasis has been on avoiding and limiting nanomaterial exposure—for example, through rules on wearing masks, providing ventilation, and monitoring aerosolized nanoparticles.

In order to establish effective safety measures, the Ministry of Economy, Technology, and Industry (Meti) has focused on hazard testing and risk assessment. It produced a study in March 2009 that suggested broad safety procedures for preventing occupational exposure to nanoparticles and recommended industry to perform voluntary safety audits and communicate information across the supply chain. The next year, the Ministry of Environment launched the Nanomaterial Information Collection and Communication Program to encourage producers to exchange danger information and develop voluntary safety measures. Meti's assessment on the programme identified six key nanomaterials: carbon nanotubes, carbon black, titanium dioxide, fullerenes, zinc oxide, and silicon dioxide. These are based on reports from 31 firms on their produced nanomaterials. The report examined the properties of each chemical, as well as its production volume and principal application in Japan, as well as exposure and emission avoidance methods.

Meti and the New Energy and Industrial Technology Development Organization collaborated on a five-year initiative to investigate and develop nanoparticle characterisation methods in order to expand scientific understanding about the hazards presented by nanomaterials. It was completed in February 2011 and focused on producing risk assessments for nanomaterials as well as establishing a risk management policy. The study resulted in thorough risk evaluations of three nanoparticles (titanium dioxide, fullerenes, and carbon nanotubes), a report on toxicity testing of manufactured nanomaterials, and recommendations for hazard assessment testing of industrial nanomaterials in animals by respiratory exposure.

It focuses on nanomaterial exposure in goods and to develop suitable management processes from the standpoint of usage and life cycles. Following its first meeting in December 2011, a report describing three major topics of debate was issued in January 2012: hazard, exposure, and risk assessment; risk management; and definition and technical measurement. Its key conclusions were:

 • evaluation of hazard, exposure, and risk;

• risk management; and

• definition and technical measurement.

Regulatory science in Japan attempts to attain the greatest possible outcome for human health and society, as determined by suitable healthcare policy, with the goal of promptly translating research findings into practical applications. The Japanese Ministry of Health, Labour, and Welfare (MHLW), the Pharmaceutical and Medical Devices Agency (PMDA), the National Institute of Health Sciences (NIHS), and the Agency for Medical Research and Development are in charge of regulation and regulatory science in this domain (AMED). A Regulatory Science Centre was formed inside the PMDA in 2018 to promote, among other things, creative approaches to advanced medicines and technologies, including nanotechnologies, with a significant emphasis on horizon scanning to allow regulators to keep up with new advances.

• Identification of compliance requirements under various guidelines including all data requirements.​

• Data gap analysis and pre-assessment support​

• Technical documentation support​

• Pre and post submission support and technical liaison with authorities.