Commercialisation of healthcare in Japan: overview

A Q&A guide to the commercialisation of healthcare in Japan.

This Q&A provides an overview of the regulatory framework for the commercialisation of medical products in Japan. It covers the key requirements for manufacturing, advertising and selling drugs, medical devices, biological products and natural health products.

To compare answers across multiple jurisdictions, visit the commercialisation of healthcare Country Q&A tool.

This Q&A is part of the Commercialisation of Healthcare Global Guide. For a full list of jurisdictional Q&As visit www.practicallaw.com/healthcare-guide.

Takaaki Nagashima, Nobuhiro Nonaka and Steven Bryan, Nagashima Hashimoto & Yasukuni
Contents

Regulatory overview

1. What is the regulatory framework for medical products?

Legislation

The primary legal bases for Japan's healthcare system are the Law for Ensuring the Quality, Efficacy, and Safety of Drugs and Medical Devices (Drugs and Medical Devices Law) (DMDL) and various implementing guidelines. The DMDL was previously known as the Pharmaceutical Affairs Law but its name was changed and revisions took effect from 25 November 2014. The Law for Ensuring the Safety of Regenerative Therapy (The Regenerative Medicine Safety Law) covers regenerative medicine. The laws covering food include the:

  • Food Sanitation Law.

  • Health Promotion Law.

  • Food Labelling Law.

The same basic principles apply to drugs, quasi-drugs, medical devices and biological products, whereas health foods are regulated under a separate system.

Regulatory authorities

The Ministry of Health, Labour and Welfare (MHLW) is in charge of public health and the regulation of the healthcare system. Bureaus within the MHLW handle specific regulatory matters.

The MHLW has given the power to issue manufacturing, sales and industry licences to local governments. There are also certain types of pharmaceutical products for which the MHLW has assigned approval power to local governments.

The Pharmaceuticals and Medical Devices Agency (PMDA) was established in 2004 as an independent regulatory agency. It is involved in a wide range of regulatory activities, including clinical studies, approvals, post-marketing reviews and pharmaceutical safety. The PMDA offers consultations on clinical trials of new drugs and medical devices.

The PMDA is the point of entry for businesses looking to sell drugs and medical devices in Japan and provides advice on product classifications and approvals. The PMDA and local governments are also available to consult with companies about drug and medical device regulations.

The PMDA divides its work among several specialised offices dealing with specific topics, including offices dealing with generic drugs and medical devices.

For more information on the MHLW and PMDA see box: The regulatory authorities.

Private parties

There are numerous private contract research organisations that assist pharmaceutical companies with clinical trials and other pharmaceutical development matters. Smaller companies without extensive regulatory and clinical trial operations tend to use such organisations. Contract research organisations typically offer:

  • Clinical trial monitoring services.

  • Data management services.

  • Statistical analysis for clinical trial results.

There are also numerous companies that offer specialised pharmaceutical consulting services to companies (Japanese and non-Japanese) covering regulatory compliance, personnel support, product development and other matters.

 
2. What types of medical products are regulated?

The Drugs and Medical Devices Law (DMDL) sets out five categories of pharmaceutical products:

  • Drugs (Article 2.1, DMDL).

  • Quasi-drugs (Article 2.2, DMDL).

  • Medical devices (Articles 2.4 to 2.8, DMDL).

  • Regenerative therapy and related products (Article 2.9, DMDL).

  • Cosmetics (Article 2.3, DMDL).

Drugs are further subdivided into:

  • Pharmacy drugs (Article 4.5.2, DMDL).

  • Drugs requiring guidance (behind-the-counter drugs) (Article 4.5.3, DMDL).

  • General purpose (over-the-counter) drugs (Article 4.5.4, DMDL).

Pharmacy drugs are, broadly, pharmaceuticals other than over-the-counter or behind-the-counter drugs (Article 4.5.2, DMDL). Specifically, they include ethical (prescription) drugs (Article 49.1, DMDL). Ethical (prescription) drugs are further divided into patented and generic varieties. Over-the-counter drugs are divided into three levels depending on the risk of potential damage to health (Article 36-7.1, DMDL). The DMDL generally treats in vitro diagnostic drugs as medical devices (Articles 2.14, 23-2.1, 23-2-3.1, 23-2-4 and 23-2-5.1).

Medical devices are divided into classes (I to IV) based on their perceived risk according to the Global Harmonisation Task Force categories:

  • Classes III and IV include devices having a "major effect" on "life and health" (Article 2.5, DMDL).

  • Class II includes devices having the potential of serious dysfunction or risk of life (Article 2.6, DMDL).

  • Class I includes devices with a minor impact on the human body even in the event of malfunction (Article 2.7, DMDL).

Under the pre-2014 Pharmaceutical Affairs Law regime, software was not treated separately as a medical device. The DMDL revisions now provide for consideration of software programs themselves as medical devices (Article 2.18).

Regenerative therapy and related products fall into three categories:

  • Cellular material used for reconstruction, repair or formation of body structure or function (regenerative therapy products) (Article 2.9.1, DMDL).

  • Cellular material used for prevention or treatment of illness (cell therapy products) (Article 2.9.1, DMDL).

  • Human genetic material used for treatment of illness (gene therapy products) (Article 2.9.2, DMDL).

Regenerative therapy is a distinct category, separate from drugs and medical devices (Articles 2.1.2, 2.1.3 and 2.4, DMDL).

Quasi-drugs are products with "mild effects" for products (Article 2.2, DMDL):

  • Preventing nausea or similar discomfort.

  • Stopping breath or body odour.

  • Preventing rashes or skin irritation.

  • Preventing hair loss or promoting hair growth.

  • Killing or repelling mice, bees, mosquitoes, and so on with the goal of protecting humans or other animals.

  • Otherwise designated by the Ministry of Health, Labour and Welfare (MHLW).

 

Drugs

3. What are the general requirements for a drug to be manufactured, advertised and sold?

Manufacturing

The manufacture of drugs can be subject to one or more of the following:

  • Manufacturing/sales approval (seizohanbai shonin) (Article 14.1, Drugs and Medical Devices Law (DMDL)).

  • A manufacturing/sales business licence (seizohanbaigyo kyoka) (Article 12.1, DMDL).

  • A manufacturing business licence (seizogyo kyoka) (necessary for manufacturing, but also for labelling and storage even without manufacturing) (Article 13.1, DMDL).

  • A foreign manufacturer accreditation (nintei) for overseas manufacturers (Article 13-3, DMDL).

Approvals only apply to the products, whereas licences apply to companies or manufacturing facilities. The second and third bullets above apply to companies or facilities within Japan.

Approval under the DMDL. The Pharmaceuticals and Medical Devices Agency (PMDA) is responsible for approving drugs. It issues approvals based on effectiveness and safety in treating, diagnosing or preventing disease. Article 40 of the DMDL Enforcement Regulations set out the documents required to be submitted to the PMDA for approval. Different drug types require different documents to be submitted.

Licences. Licences apply to sellers and manufacturers of drugs. Licences are granted based on the applicant's quality control and safety management ability and include:

  • Manufacturing/sales business licences, for manufacturers.

  • Manufacturing business licences.

The manufacturing/sales business licence applies to non-retail sales by a manufacturer, not to manufacturing. It allows the holder to import and sell drugs manufactured by the licence holder or a foreign manufacturer accreditation holder (Article 2.13, DMDL). Although it is a licence for sale, this type of sales licence applies only to manufacturers, not drug stores or other retailers.

There are different licences for prescription drugs and non-prescription drugs (Articles 12.1 and 49.1, DMDL,) and the licence requirements differ depending on the type of licence (Article 12-2, DMDL). It is common for the manufacturing/sales business licence holder to apply for approval of the drugs it manufactures or imports.

The 2014 DMDL revisions added requirements for licence holders manufacturing particularly risky drugs to make special reports to the Ministry of Health, Labour and Welfare (Article 52-2.1, DMDL) and on their websites (Article 52-2-.2, DMDL).

The DMDL sets out five manufacturing categories:

  • Biological products and other drugs requiring special manufacturing and quality control attention.

  • Radiopharmaceuticals.

  • Sterile drugs.

  • Drugs other than those covered by the above three categories.

  • Packaging, labelling and storage only.

The buildings and facilities standards (Ministerial Ordinance No 2, 1961) and good manufacturing practice (Ministry of Health, Labour and Welfare Ministerial Ordinance No 179, 24 December 2004) also apply. The manufacturing business licence holder must have on its staff a pharmacist or other individual with similar knowledge as a responsible technical employee (Article 17.1, DMDL).

Foreign manufacturer accreditation. For drugs manufactured overseas, a foreign manufacturer accreditation is required, rather than a manufacturing business licence. To obtain the foreign manufacturer accreditation, foreign manufacturers must meet the same requirements as manufacturers in Japan. When necessary, Ministry of Health, Labour and Welfare officials can inspect manufacturing facilities located outside of Japan (Article 13-3.3, DMDL).

Special approvals. There are special procedures for fast-track approval reviews that apply both to drugs and medical devices, as well as special procedures for overseas companies seeking approval in Japan:

  • Fast-track review system (Article 14.7, DMDL). Drug approval reviews are normally processed in the order received. There is, however, a fast-track review system for orphan drugs and other drugs that are considered especially important. The two criteria for the fast-track review are the seriousness of the targeted disease and the medical usefulness of the drug or device (Article 14.7, DMDL; Notification No 0901-(1), Ministry of Health, Labour and Welfare, Food and Drug Administration Evaluation and Licensing Division, 1 September 2011).

  • Orphan drugs and medical devices (Articles 2.16, 14.7 and 77-2, DMDL). Japan has had policies in place to promote research and development into orphan drugs and medical devices since 1993. The criteria include relevance to fewer than 50,000 indicated patients and medical utility.

  • Emergency approval (Article 14-3, DMDL). There is an approval system for emergency drugs and medical devices used to prevent infectious diseases having a major effect on public health. This approval system applies to drugs for diseases for which the drug is the only method of treatment and is already marketed outside of Japan (in North America, the EU or similar regions). These products can be granted emergency approval by the Minister of Health, Labour and Welfare without going through the ordinary approval review procedures.

  • Designated marketing approval holder (DMAH) system (Article 19-2, DMDL). This is a special procedure for overseas companies seeking approval in Japan.

Foreign pharmaceutical manufacturers can apply under their own name for drug approval if they perform the required quality, efficacy and safety studies and undertake the necessary application procedures. But the overseas manufacturer will need to appoint a DMAH, which is a manufacturing/sales business licence holder in Japan with a licence corresponding to the approved product (Article 19-2.3, DMDL). The appointed DMAH will be responsible for health and hygiene-related issues and can also undertake marketing in Japan.

In practice, there are three basic ways for a non-Japanese company to obtain approval for pharmaceuticals manufactured overseas:

  • Option 1: establish a Japanese corporation that obtains the necessary approvals and licences. This provides the most durable presence in Japan and gives the foreign company the most control. It also entails the most initial time and expense (including hiring staff) and must be done in compliance with the provisions of the DMDL.

  • Option 2: designate an existing Japanese company to obtain the necessary approvals and licences. The manufacturing/sales approval for the drug will be registered in the Japanese company's name. This can raise potential problems if the overseas company does not strictly control the Japanese approval holder.

  • Option 3: use the DMAH system and select a Japanese company approved by the Ministry of Health, Labour and Welfare (MHLW) to act as a DMAH. This option provides several benefits, including the manufacturing/sales approval being held directly by the non-Japanese company. In addition, the costs for obtaining/maintaining drug approval are lower than for the first two options. Since the approval is in the non-Japanese company's name, there are fewer concerns about the Japanese company acting on its own. If there are problems with the DMAH, the non-Japanese company can designate another company as the DMAH. Compared with the first option, the costs for a DMAH are lower, since there is no need to establish a new company. DMAHs are authorised by the MHLW, licensed for manufacture/sales of pharmaceuticals and provide full support in the drug approval process.

Exceptions. Drugs determined by the MHLW to be low risk do not need manufacturing/sales approval (Ministry of Health, Labour and Welfare Bulletin No 104, March 28, 1994). Drug approval is not necessary for research and clinical trials subject to specific MHLW standards (Articles 2.17 and 80-2, DMDL). Individuals and physicians can also import unapproved drugs for their own use or use with their patients subject to certain restrictions. The definition of clinical trials under the DMDL is narrow and limited (Article 2.17). In addition, clinical trials are subject to compliance with the MHLW's clinical trial standards for good clinical practices (Article 80-2, DMDL).

There are currently no provisions for compassionate use for pharmaceuticals in Japan.

Advertising

See Question 8.

Sale

Sellers must have either a:

  • Licence to open a pharmacy under Article 4.1 of the DMDL.

  • Drug sales licence under Article 25 of the DMDL.

There are three types of licence corresponding to different types of sales:

  • Retail sales (Article 25.1, DMDL).

  • Placement sales (Article 25.2, DMDL).

  • Wholesale (Article 25.3, DMDL).

A wholesale licence only allows the wholesaler to sell to customers with pharmacy or drug sales licences (Article 25.3, DMDL).

Pharmacy drugs can only be sold by pharmacists in licensed pharmacies (Article 36-3, DMDL). Drugs requiring guidance (behind-the-counter drugs) can only be sold by pharmacists in licensed pharmacies or in stores with a retail sales licence (Article 36-5, DMDL). General purpose (over-the-counter) drugs are sold by licensed pharmacies, retail sales licence holders and placement sales licence holders (Article 36-9, DMDL). Only pharmacists can sell the highest of the three risk levels of general purpose (over-the-counter) drugs.

Sales of behind-the-counter drugs require face-to-face disclosure of written information (Articles 36-4.1 and 36-6.1, DMDL). Accordingly, they cannot be sold over the internet, by post or through a catalogue. Over-the-counter drugs can be sold over the internet, by post or through a catalogue by holders of pharmacy and retail sales licences (Articles 4-3-4 and 26-3-5, DMDL).

 
4. Are there different requirements for patented and generic drugs?

The approval and licence requirements are the same for generic and patented drugs. However, the time for approval of generic drugs is generally shorter due to prior approval of the patented drugs.

The basic safety, advertising, and regulatory rules are the same for patented and generic drugs.

The standard patent term is 20 years from the time of application. If the patent cannot be enforced because necessary approval has not been obtained, the patent term can be extended for a maximum of five years to cover the period of non-use (Article 67.2, Patent Law).

Generic drugs will not be approved until the patent has expired. Partial approvals for indications, dosage, and administration not covered by the patent are permitted (Notification No 0605014, Ministry of Health, Labour and Welfare, Food and Drug Administration Evaluation and Licensing Division, 5 June 2009).

 
5. What authority is responsible for regulating the manufacture, advertising and sale of drugs?

The Ministry of Health, Labour and Welfare (MHLW) regulates the manufacture, advertising and sale of drugs. The MHLW's Food and Drug Compliance and Narcotics Division and local government drug inspection guidance divisions are generally in charge of ensuring compliance with the Drugs and Medical Devices Law (DMDL). They are also in charge of compliance with advertising regulations.

For more information on the MHLW see box: The regulatory authorities.

 
6. Are there fewer or different requirements for drugs that have already been licensed/approved in another jurisdiction?

Approvals are required for drugs that have been licensed/approved in other jurisdictions. Approval overseas does not exempt drugs from Japanese approval requirements, except under the emergency approval system (see Question 3, Manufacturing).

However, data from overseas clinical trials can be used as bridging studies for the Japanese approval process.

 
7. Is it possible to sell drugs to or buy drugs from other jurisdictions?

Drugs approved in Japan can be exported. Japanese approval requirements apply to drugs that have been licensed/approved in other jurisdictions. Overseas approval does not exempt drugs from Japanese approval requirements.

There are special regulations covering drugs for export (Article 80, Drugs and Medical Devices Law (DMDL)). The manufacture of drugs for export requires a form to be submitted to the Ministry of Health, Labour and Welfare (Article 80.6, DMDL; Article 74.1, DMDL Enforcement Order). As with all drugs, the manufacturer will also need a manufacturing business licence. Labelling and information insert requirements are those that are set out in the jurisdiction of import. Generally, only drugs that have manufacturing/sales approval from the Ministry of Health, Labour and Welfare (MHLW) can be imported into Japan. At the time of importation, the holder of the manufacturing/sales business licence must file an import notice with the regional Bureau of Health and Welfare.

Individuals can generally purchase drugs from other jurisdictions for their own use. Where there is no substitute drug approved in Japan, physicians can also individually import drugs for use with their patients. The importation of certain drugs and quantities exceeding certain amounts, even for individual use, requires a certificate for import to be submitted to the Regional Bureau of Health and Welfare.

 
8. Is it permitted to advertise drugs to consumers? Are there restrictions on advertising?

Advertising is prohibited for all ethical (prescription) drugs (Pharmaceutical Code of Advertising Practices, Ministry of Health, Labour and Welfare, Pharmaceutical Affairs Director Notice No 1339, 9 October, 1980).

In addition, Article 66 of the Drugs and Medical Devices Law (DMDL) prohibits false and exaggerated advertising. There are rules covering what claims are permissible for approved and non-approved products.

Only products approved as drugs and medical devices can advertise and make claims that the product either (Article 68, DMDL):

  • Treats, improves or prevents illness.

  • Strengthens or promotes human tissue function.

These restrictions are extremely broad and include references to trade names, catch phrases, ingredients, manufacturing processes, origins/sources, media articles, excerpts from medical interviews, and so on (Pharmaceutical Code of Advertising Practices, Ministry of Health, Labour and Welfare, Pharmaceutical Affairs Director Notice No 1339, 9 October 1980; Ministry of Health, Labour and Welfare, Pharmaceutical Affairs Bureau Inspection and Guidance Division, No 121, 9 October 1980).

The following require prior approval:

  • Claim potential improvement in specific areas of the body.

  • Mention the treatment of illness.

  • Signal the effects of treatment.

  • Quote from experience or research organisations.

  • Imply physical improvement.

  • Discuss the origins of components or ingredients that imply medical treatment.

Information qualifies as "advertising" if it (Article 68, DMDL):

  • Is clearly intended to attract customers.

  • Highlights a specific product name.

  • Could come to the attention of the general public.

This includes the packaging and attached written materials, leaflets/handouts, presentation in TV commercials, and so on. Product descriptions and presentations of users' opinions and experiences count as advertising.

Under the Unjustifiable Premiums and Misleading Representations Act (Misleading Representations Act), it is illegal to give the impression that a product is notably superior than it really is.

The Consumer Affairs Agency (CAA) is responsible for determining whether there has been a violation of the Misleading Representations Act. The CAA can require the seller to submit evidence supporting the product claims (Article 4.2, Misleading Representations Act). Failure to submit the requested evidence results in the claims being held to be misleading. The seller will need to remove all claims found to be misleading by the CAA.

The Misleading Representations Act and the DMDL are distinct laws. Therefore, even if a claim does not violate the Misleading Representations Act, it may still fall foul of the DMDL.

 

Medical devices

9. What are the general requirements for a medical device to be manufactured, advertised and sold?

Manufacturing

Under the Drugs and Medical Devices Law (DMDL), a medical device is an instrument or apparatus intended for use diagnosing, curing or preventing diseases in humans or animals, or intended to affect the structure or function of human or animal bodies (Article 2.4). Even where the device is simple, it is considered as a medical device if it is used in diagnosing, curing or preventing disease.

The basic requirements for manufacturing medical devices are similar to those for drugs, but in some cases rather than licences (or accreditations), registration is required (including manufacturing industry registration and foreign manufacturer registration). This avoids the need, for example, for inspection of facilities (Articles 13.4.1, 13.5, and 23-2-3.4, DMDL).

The manufacture and distribution of medical devices is subject to receipt of:

  • Manufacturing/sales approval (Article 23-2-5.1, DMDL).

  • A manufacturing/sales business licence (Article 23-2.1, DMDL).

  • Manufacturing industry registration (Article 23-2-3.1, DMDL).

  • Foreign manufacturer registration, if manufactured overseas (Article 23-2-4.1, DMDL).

Approvals apply to the products, while licences or registrations only apply to the company or manufacturing facility. The manufacturing/sales business licence holder must comply with manufacturing and quality control system standards (Article 23-2-2.1, DMDL) and good vigilance practices set out by the Ministry of Health, Labour and Welfare (MHLW) (Article 23-2-2.2, DMDL).

There have been frequent problems with companies manufacturing and selling under the wrong product category. In particular, various beauty, health, and emergency medical services products have been sold in Japan as consumer electronics, and the MHLW subsequently determined that they should have received approval as a medical device.

Manufacturing/sales approval (medical device approval). As with drugs, in principle, the manufacture and sale of medical devices requires approval (Article 23-2-5-1, DMDL). However, for low risk, class I devices, approval is not necessary. A basic submission amounting to self-approval will suffice, in the form of a "manufacturing/sales notice" submitted to the Pharmaceuticals and Medical Devices Agency (PMDA) (Article 23-2-12.1, DMDL). For certain class II devices (managed care devices) and class III devices (that is, certain medical devices requiring a high level of care for which approval guidelines have been issued), an "approval" from a registered third party attesting to compliance with the relevant guidelines is sufficient (Article 23-2-23.1, DMDL). For products with greater risk, the documentation required is more substantial.

In practice, an applicant for manufacturing/sales approval will usually already have the relevant licence (Article 23-2-5.2.1, DMDL). Manufacturing/sales approvals are subject to a quality management system and an inspection of the manufacturing facilities and equipment (Articles 23-2-5.2.4 and 23-2-5.6, DMDL).

In the past, every manufacturing location required a quality management system inspection. The 2014 DMDL revisions simplified this requirement to an inspection of the quality management system in its entirety (Articles 23-2-5.6 and 23-2-23.3, DMDL). The 2014 revisions also simplified the previous requirement for inspections per product to inspections per product type (Articles 23-2-5.7 and 23-2-23.4, DMDL).

Manufacturing/sales business licence. A manufacturing/sales business licence is necessary to import and sell medical devices (Article 23-2.1, DMDL). There are different licence types corresponding to different types of medical devices (Article 23-2.1, DMDL):

  • The first type is applicable to all medical devices.

  • The second type is for managed care and general use medical devices (classes I and II) only.

  • The third type is for general use medical devices (class I) only.

The type of licence and the documentation necessary to obtain the licence vary for each type of medical device.

Manufacturing industry registration (manufacturing and storage). Manufacturing industry registration is necessary for all businesses manufacturing, packaging/labelling or storing medical devices (Article 23-2-3.1, DMDL). Even if the product is manufactured and packaged outside of Japan, the distributor must register, as it will be responsible for storing the product in Japan after import.

Under the pre-November 2014 system, the manufacturing industry registration was a licence and included compliance with buildings and facilities standards (Ministerial Ordinance No 2, 1961). This requirement does not apply under the post-November 2014 system (Article 23-2-3.4, DMDL).

Advertising

Advertising requirements are the same as for drugs (see Question 8).

Sale

Retailers selling medical devices are subject to licence requirements. A licence is necessary for the sale or lease of high risk, specially controlled medical devices (class III and IV medical devices and some class II devices) (Article 39.1, DMDL).

Local governments are responsible for reviewing applications and granting licences (Article 39.2, DMDL). For class II devices not subject to licence, sale and lease is subject to filing a notice with the local government (Article 39-3.1, DMDL). No licences or filings are necessary for class I medical devices, but the seller has the same management obligations as for class II devices (Article 40.3, DMDL).

The repair of medical devices also requires a licence (Article 40-2.1, DMDL).

 
10. What authority is responsible for regulating the manufacture, advertising and sale of medical devices?

The regulatory authorities are the same as for drugs (see Question 5), but the Ministry of Health, Labour and Welfare (MHLW) and local governments have separate compliance divisions for drugs and medical devices.

For more information on the MHLW see box: The regulatory authorities.

 
11. Are there fewer or different requirements for medical devices that have already been licensed/approved in another jurisdiction?

The requirements are the same regardless of licences/approvals in other jurisdictions, except under the emergency approval exception (Article 23-2-8.1, DMDL). However, the process will normally be quicker if similar products have already been approved within Japan.

If similar products have not already been approved in Japan, the data collection process for approval may in practice be reduced if the applicant already has sufficient data from other jurisdictions. Although data collected overseas for drug approvals can cause problems, data from non-Japanese clinical trials for medical devices can generally be used without difficulty.

 
12. Is it possible to sell devices to or buy devices from other jurisdictions?

The rules are the same as for drugs (see Question 7). The importer must have a manufacturing/sales business licence and the medical device must have Japanese approval. The importer must also file an import notice.

As with drugs, individuals can buy from overseas for their own use. Physicians can also purchase medical devices from other jurisdictions for use with their own patients. A certificate must also be submitted when quantities exceed a certain limit.

 
13. Is it permitted to advertise medical devices to consumers? Are there restrictions on advertising?

The rules are the same as for drugs (see Question 6). However, there is a recurring problem with companies selling devices as general consumer goods when they are, in fact, required to have medical device licences and approvals.

 

Biological products

14. What are the general requirements for a biological product to be manufactured, advertised and sold?

Requirements differ depending on whether a biological product is a regenerative therapy product-related product or not.

Non-regenerative drugs and medical devices

Within the drug and medical device categories, biological drugs and medical devices manufactured using biological materials require special care (Articles 2.10 and 2.11, Drugs and Medical Devices Law (DMDL)). The Ministry of Health, Labour and Welfare (MHLW) will designate a product as biological after it consults with its Pharmaceutical Affairs and Food Sanitation Council (Articles 2.10, 2.11, DMDL).

Japan sets higher regulatory standards for biological products than for ordinary drugs and medical devices. As with non-biological drugs and medical devices, the approvals/licences apply (see Questions 3 and 9). However, requirements for the manufacturing business licence are more stringent. Manufacturing and quality control rules are also more stringent.

Manufacturing control requires the presence of a:

  • Pharmacist (Article 17.3, DMDL).

  • Doctor or technician with knowledge of bacteriology (Article 68-16.1, DMDL).

The DMDL also contains more stringent requirements for manufacture, distribution, and use (Articles 68-17 to 68-25, DMDL), including requirements for records to be traceable from donors to users (Articles 68-22, DMDL).

Manufacturing standards for biological products cover requirements for facilities, equipment, manufacturing methods and quality control. Other biological standards address the manufacture of drugs and medical devices. Holders of biological product approvals must submit infection reports to the MHLW every six months, evaluating their products based on the latest reports of infections caused by raw materials used in their products (Article 68-24, DMDL).

For certain biological products, the MHLW requires additional precautions to reduce the risk of infection transmission, including prescribed methods of collecting and processing source materials and record keeping. The MHLW also specifies procedures for donor screening, such as oral questionnaires and viral testing at the time of cell or tissue collection.

Records relating to source materials that have a higher potential risk for transmitting infectious agents must be kept and stored in accordance with MHLW's safety measure ordinances (Article 68-22, DMDL).

Advertising requirements are the same as for drugs and medical devices (see Question 8).

Regenerative therapy and related products

The DMDL classifies regenerative therapy products separately from drugs or medical devices. Regenerative therapy and related products are generally treated in the same way as drugs. Manufacturing/sales approval (Article 23-25.1, DMDL), manufacturing/sales, manufacturing industry, and sales licences are all required (Articles 23-20.1, 23-22.1 and 40-5.1, DMDL).

Unlike drugs, it is possible to obtain special early approval with conditions or a time limit for non-homogenous regenerative therapy products for which efficacy is estimated (Article 23-26.1, DMDL). Efficacy and safety are subject to further inspection after the conditional/limited approval expires (Article 23-26.3, DMDL). The aim is to promote safe and rapid adoption of regenerative therapies.

When using regenerative therapy products, physicians must obtain the informed consent of the patient (Article 68-4, DMDL). As with other non-regenerative biological products, periodic reports are required for infectiousness (Article 68-14, DMDL) and patient records must be kept (Article 68-7, DMDL).

The Regenerative Therapy Safety Law came into effect in November 2014 and classifies regenerative medicines into separate categories based on the degree of impact to human life and health, with separate procedures required for each (Articles 4, 8.1, and 9). Physicians (including dentists) performing regenerative medicine must obtain informed consent from the patient (Articles 13 and 14, Enforcement Regulation of the Regenerative Therapy Safety Law). The Regenerative Therapy Safety Law requires a licence (Article 35.1) or notification (Article 40.1) for all cellular material used for regenerative medicine.

Advertising requirements are the same as for drugs and medical devices (see Question 8).

 
15. What authority is responsible for regulating the manufacture, advertising and sale of biological products?

The Ministry of Health, Labour and Welfare (MHLW) regulates the manufacture, advertising and sale of biological products. The MHLW and local governments are available to provide guidance to the drug/medical device approval holder and other parties about such products (Articles 68-8 and 68-23, Drugs and Medical Devices Law (DMDL)). The Pharmaceuticals and Medical Devices Agency (PMDA) can also require the approval holder to collect information in response to infectious disease reports, in addition to the required six-monthly reports (Articles 68-14.1 and 68-24.1, DMDL).

For more information on the MHLW see box: The regulatory authorities.

 
16. Are there fewer or different requirements for biological products that have already been licensed/approved in another jurisdiction?

The rules are the same as for drugs and medical devices (see Questions 6 and 11). There is no particular relaxation of requirements simply due to licence or approval in another jurisdiction. In practice, the approval of similar products in Japan tends to reduce the amount of new information required and the time taken for approval. The applicant can also, in practice, find its data-gathering burden reduced if it already has information gathered for its foreign licence/approval.

 
17. Is it possible to sell biological products to or buy biological devices from other jurisdictions?

As for drugs and medical devices, doctors can personally import biological products for use with their patients subject to limitations on quantity. Imports of vaccine require approval from the Ministry of Economy, Trade and Industry and import quota (import trade control order) approval from the Ministry of Health, Labour and Welfare (MHLW).

 
18. Is it permitted to advertise biological products to consumers? Are there restrictions on advertising?

There are special labelling and insert requirements for biological products (Articles 65-2, 65-3, 68-17 and 68-18, Drugs and Medical Devices Law (DMDL)). For certain specified biological products derived from human tissue with a high infection risk, the manufacturer must provide the user with an explanation of the benefits and risks (Articles 2.11 and 68-21, DMDL).

 

Natural health products

19. Is there a category for natural health products (including, for example, traditional medicines, homeopathic medicines, supplements, vitamins and minerals)?

Japan has specific regulations for "food with health claims" (see Question 20). The Consumer Affairs Agency (CAA), not the Ministry of Health, Labour and Welfare (MHLW), is responsible for administering this system.

 
20. What are the general requirements for natural health products to be manufactured, advertised and sold?

In addition to general food regulations and the Food Safety Law, there is a "food with health claims" category that allows a seller to make certain kinds of specific health-related claims not allowed for regular foods. These requirements are fairly complex, strict and only cover very specific categories of products.

Food with health claims are subject to the provisions of the:

  • Food Labelling Law.

  • Health Promotion Law.

  • Food Sanitation Law.

Labelling and advertising of food with health claims are regulated by the:

  • Drugs and Medical Devices Law (DMDL).

  • Food Labelling Law.

  • Health Promotion Law.

  • Food Sanitation Law.

  • Misleading Representations Act.

Products that are not specifically approved to make particular drug claims cannot make such claims in their advertising.

Foods with health claims are divided into three categories:

  • "Food for specified health uses" (a sub-category of "food for special dietary uses" (FOSDU)) which must have specific, individual approval from the Consumer Affairs Agency (CAA).

  • "Food with nutrient function claims" is food that meets normal standards. It does not need a licence or approval, but simply needs a label indicating that the standards established by the CAA have been satisfied.

  • "Food displaying function claims" is food displaying safety and functionality claims that have been sent to the CAA prior to sale. Such claims are meant to be supported by science.

Food for specified health uses

Foods for specified health uses are products that have received approval from the CAA. They can be labelled as containing health-promoting ingredients that can be expected to have specific effects on physiological function. These products are allowed to claim on their labels that they maintain or improve particular bodily functions. Examples of such claims may be "improves bowel movements" or "promotes the breakup of body fat". Claims relating to treatment or improvement of symptoms or illnesses are not generally permitted.

Food for specified health uses must be labelled as such and put on the market for sale only after receiving specific approval from the CAA. There must be an inspection of the scientific basis for the effectiveness and safety of the product based on its health claims and effects on physiological function (Article 26.1, Health Promotion Law). Food products that have received approval can carry a mark indicating this.

Under the guidelines set out by the CAA (October 30, 2014, CAA Food Labelling, No. 259), approval as a food for specified health uses will be granted once a list of various health and safety requirements have been fulfilled (Article 26.2, Health Promotion Law). Product labels must accurately indicate that the product is useful in maintaining or improving health and must clearly avoid any confusion with pharmaceutical products.

Food for specified health uses are a sub-category of food for special dietary uses. These are food products labelled as appropriate for use with infants, children and individuals who are ill or pregnant. FOSDU products can use medical and nutritional expressions to indicate that they are appropriate for use in promoting growth or maintaining or recovering health among infants, children, the infirm and pregnant women. For example, wording can include "appropriate for patients on protein-restricted diets (such as kidney patients)", or "appropriate for diabetic diets". FOSDU cannot use expressions indicating that they can be used to treat disease. Since their use is restricted, FOSDU requires authorisation by the CAA (Article 26.1, Health Promotion Law). As with food for specified health uses, FOSDU products are allowed to carry a CAA authorisation seal.

Food with nutrient function claims

Food with nutrient function claims are products that include specified nutritional components and are allowed to indicate on their labels the function of those nutritional components in accordance with standards established by the CAA (Article 31, Health Promotion Law). These foods are meant to serve as dietary supplements for the elderly or others who are unable to maintain a regular diet or who are otherwise unable to obtain their necessary daily nutritional requirements.

Products that are sold as food with nutrient function claims must indicate on their labels:

  • That they have not been subject to individual inspection by the CAA.

  • Warnings.

  • That they include nutritional components in compliance with standard allowances.

  • Nutritional use statements.

If the above requirements are met, products can be developed, manufactured and sold as food with nutrient function claims without filing an application for governmental approval or authorisation.

Nutritional elements that can be indicated on the labels of food with nutrient function claims are those essential nutrients for physical function whose chemical basis is widely recognised both medically and nutritionally. Currently, these include the following minerals and vitamins:

  • Minerals: calcium, zinc, copper, magnesium and iron.

  • Vitamins: niacin, pantothenic acid, biotin, vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E and folic acid.

The following cannot be included on labels for food with nutrient function claims:

  • Nutritional components that have not been recognised by the CAA for inclusion on nutrient labels.

  • Specific health claims authorised for use with food for specified health uses (for example, "aids digestion").

  • Expressions that may lead to the false impression that the product is acting as a pharmaceutical and which are related to the diagnosis, treatment or prevention of disease.

Food displaying function claims

Food displaying function claims are foods for which the seller/manufacturer is allowed to present certain data-based claims on the product label. There is no special approval or certification required from the CAA.

This new category came into effect on 1 April 2015 under the Food Labelling Law (2013, No. 70) and Food Labelling Standards (2015, No. 10). The CAA published guidelines concerning these foods on 30 March 2015.

Food displaying function claims are defined as foods displaying on their labels scientifically-based information that their ingredients can be expected to promote or support health (Article 2.1.10, Food Labelling Standards). Manufacturers that wish to include these types of health claims on their labels must submit to the CAA at least 60 days prior to commencement of sales:

  • The proposed claims.

  • Basic information on the applicant.

  • Information on safety and functionality.

  • Information on manufacturing and quality control processes.

  • Information on systems for gathering data about adverse health effects.

There are various restricted categories of foods and target consumers that are excluded from the food displaying function claims system, including:

  • FOSDU (see above, Food for specified health uses).

  • Food with nutrient function claims (see above, Food with nutrient function claims).

  • Alcohol.

  • Products marketed for minors, pregnant women, nursing mothers and individuals suffering from illnesses.

 
21. What authority is responsible for regulating the manufacture, advertising and sale of natural health products?

The Consumer Affairs Agency (CAA) regulates the advertising and sale of food with health claims. Local health authorities oversee food manufacture.

The Ministry of Health, Labour and Welfare (MHLW) has authority to determine whether a product is a pharmaceutical product or food with health claims.

For more information on the CAA and MHLW see box: The regulatory authorities.

 
22. Are there fewer or different requirements for natural health products that have already been licensed/approved in another jurisdiction?

The same requirements apply for food with health claims that have been licensed/approved in another jurisdiction.

 
23. Is it possible to sell natural health products to or buy natural health products from other jurisdictions and/or electronically?

It is possible to sell and/or buy products from other jurisdictions and/or electronically. However, such products must comply with all applicable requirements.

For imports into Japan (other than for personal use), the importer must confirm that all ingredients are allowed in Japan and that the product does not qualify as a drug under Japanese law. For food, all ingredients (including additives) must be checked against the Food Sanitation Law to see if they are allowed in Japan. The importer must also file a report with the quarantine officials.

As for drugs and medical devices, individuals can import food products for their own use.

 
24. Is it permitted to advertise natural health products to consumers? Are there restrictions on advertising?

Food with health claims can be advertised directly to consumers, subject to the provisions of the:

  • Drugs and Medical Devices Law (DMDL).

  • Food Labelling Law.

  • Health Promotion Law.

  • Food Sanitation Law.

  • Misleading Representations Act.

There have been cases involving violations where manufacturers/sellers have advertised food products using drug claims in violation of the DMDL.

 

Reform

25. Are there any plans to reform the rules on the development, manufacture, advertising and sale of medical products?

Recent and proposed reforms include the following:

  • New regulations on falsified medicinal products, rules of good distribution practice for medicinal products and export to other countries have been introduced in the first months of 2015. These regulations implement EU directives in this field and introduce:

    • new obligations for entrepreneurs, especially concerning the management of a supply chain;

    • a prohibition on pharmacies from selling medicinal products to other entities (other than patients); and

    • an obligation to notify the Main Pharmaceutical Inspector (MPI) when exporting/selling medicinal products abroad.

In the upcoming months, the Ministry of Health, is expected to introduce amendments to the Pharmaceutical Law as a result of the introduction of Regulation (EU) 536/2014 on clinical trials on medicinal products for human use. The changes are expected to mainly cover the work of ethics committees. The Ministry of Health is also working on possible solutions to provide better financing for non-commercial clinical trials.

 

The regulatory authorities

Ministry of Health, Labour, and Welfare (MHLW)

W www.mhlw.go.jp

Principal responsibilities. The MHLW is Japan's cabinet ministry in charge of food and drug laws and issues, as well as pensions, labour, and other social welfare matters.

Pharmaceuticals and Medical Devices Agency (PMDA)

W www.pmda.go.jp

Principal responsibilities. The PMDA works with the MHLW and is responsible for ensuring the safety and quality of pharmaceuticals and medical devices.

Consumer Affairs Agency (CAA)

W www.caa.go.jp

Principal responsibilities. The CAA is responsible for consumer protection.



Online resources

MHLW database

W www.hourei.mhlw.go.jp/hourei

Description. Official database service of the MHLW providing access to MHLW-related law, announcements, guidelines, and so on. Maintained and kept up-to-date by the MHLW.

Consumer Affairs Agency (CAA)

W www.caa.go.jp/soshiki/legal/index.html

Description. Official CAA website providing access to CAA-related laws, orders, and cabinet office ordinances. Maintained and kept up-to-date by the CAA.

Japanese law translation database

W www.japaneselawtranslation.go.jp/; www.japaneselawtranslation.go.jp/?re=02

Description. Official website of the Ministry of Justice providing access to translation of Japanese laws. All translations are for guidance only.



Contributor profiles

Takaaki Nagashima

Nagashima Hashimoto & Yasukuni

T +81 3 3239 5750
F +81 3 3239 8538
E nagashima@nandhlaw.com
W http://nandhlaw.com/

Professional qualifications. Japan; New York, District of Columbia

Areas of practice. Corporate; M&A; IP; regulatory; litigation/arbitration.

Nobuhiro Nonaka

Nagashima Hashimoto & Yasukuni

T +81 3 3239 5750
F +81 3 3239 8538
E nonaka@nandhlaw.com
W http://nandhlaw.com/

Professional qualifications. Japan

Areas of practice. Corporate; M&A; IP; regulatory; litigation/arbitration.

Steven Bryan

Nagashima Hashimoto & Yasukuni

T +81 3 3239 5750
F +81 3 3239 8538
E bryan@nandhlaw.com
W http://nandhlaw.com/

Professional qualifications. California

Areas of practice. Corporate; M&A; IP; regulatory; litigation/arbitration.


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