Marketing, Manufacturing, Packaging & Labeling, Advertising
Marketing, manufacturing, packaging & labeling, advertising in Japanese Pharma – a comprehensive legal overview. Prepared in association with Nishimura & Asahi, a leading law firm in Japan, this is an extract from The Pharma Legal Handbook: Japan, available to purchase here for USD 99.
1. What is the authorization process for the marketing of new drugs, biologics, medical devices, over-the-counter medications, and other medicinal products?
To obtain marketing authorization for new drugs, biologics and medical devices, submission of application to PMDA is required with the data of clinical trial.
The authorization processes of over-the-counter (OTC) medications differ depending on the kind of the drug, i.e. new drug/new indication, switch OTC and other OTC products. A new drug/new indication requires the same process as new drugs for prescription. A drug used in the medical market as a prescription drug for a long time, and the safety of which is established, can be approved as OTC product (switch OTC). Switch OTC is examined by the PMDA with consultation by Central Pharmaceutical Affairs Council. Most OTC products are low risk and the active ingredients are the same as those used in the market for long time. Those are examined either by local prefecture government or the PMDA.
Under PMD Act, some products are categorized as Quasi-drug. Those are examined either by local prefecture government or PMDA.
2. What is the authorization process for the marketing of generic versions of these products?
The authorization process for the marketing of generic products are same as the new drug, but for generic products, clinical trial data is not required, only stability test data and bioequivalence test data.
3. What are the typical fees for marketing approval?
Fee for a marketing authorization really depends on the type of product. For a new drug, it can be approximately 50,000,000 yen, and for a new medical device, can be approximately 20,000,000. In addition, consultation with the PMDA is required with a consulting fee.
4. What is the period of authorization and the renewal process?
There is no limit to the authorization period and thus no renewal process.
5. What are the requirements, if any, for post-approval pharmacovigilance?
There are two rules relating to post marketing surveillance (PMS). One is GPSP (Good Post-marketing Study Practice) and the other is GVP (Good Vigilance Practice). Under GPSP, marketing authorization holder must conduct treatment outcome study, special treatment outcome study and post marketing clinical trials. Under GVP, marketing authorization holder must collect safety information and take action, and conduct early post marketing phase vigilance (EPPV), which is surveillance for the first 6 months after starting sales in the market.
6. Are foreign marketing authorizations recognized?
Foreign marketing authorizations are recognized under PMD Act. The foreign marketing authorization applicant has to designate a manufacturing/marketing business license holder in Japan. If the foreign marketing authorization is granted to a foreign company, then the designated manufacturing/marketing business license holder may manufacture and sell the authorized product.
7. Are parallel imports of medicines or devices allowed?
8. What are the restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for healthcare organizations and individual medical practitioners?
Incentives are strictly restricted under industry rules.
Japan has two industry associations in the pharmaceutical industry. One is Japan Pharmaceutical Manufacturers Association (JPMA) which is a member of the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA). The other is The Fair Trade Council of the Ethical Pharmaceutical Drugs Marketing Industry (FTC). Both industry associations have rules regarding gifts and other incentives. JPMA has basically same rules as IFPMA. FTC is a Japan-specific organization which is established under the Act against Unjustifiable Premiums and Misleading Representations, one of anti-trust related laws. FTC has established the Fair Competition Code of Ethical Pharmaceutical Drugs (FCC), and FCC has detailed provisions relating to gifts and other incentives for healthcare organizations and individual medical practitioners.
The Medical Device industry has industry associations similar to the Pharmaceutical industry and similar rules apply.
9. How is the manufacturing of medicines and devices regulated and by which agencies?
The manufacturing of medicines and devices is regulated under the PMD Act and the agencies are local prefecture government, MHLW and PMDA.
10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the U.S. Food & Drug Administration and/or the European Medicines Agency?
Yes. Japan is a member of PIC/S and has MRA with EU.
11. What is the inspection regime for manufacturing facilities?
Under PMD Act, a manufacturer has an obligation to accept GMP Compliance Inspection by local prefecture government or PMDA at the time of examination of marketing authorization and within every five years thereafter.
12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?
13. What are the requirements for the storage, packaging, and handling of medicines and devices and their constituent components?
Storage, packaging and handling of medicines and devices are provided in the PMD Act and regulations. Also MHLW has announced GDP Guidelines in January 2019, which is harmonized with PIC/S GDP Guideline. Thus, storage, packaging and handling of medicines and devices are now harmonized with global standards.
14. What information must be included in medicine and device labeling?
The PMD Act provides the information to be included in labeling (package inserts). MHLW has also issued package insert notification to provide guidelines. According to the PMD Act, the package insert must include, among others, the name, warning, contraindication, composition and properties, indication and efficacy, usage and administration, usage notes (including adverse events, combination use and use to pregnant women, children or senior people), and other information specified in law.
15. What additional information may be included in labeling and packaging?
What information “may” be included is not specified, but any false, exaggerated or misleading information is prohibited to be included in labeling and packaging.
16. What items may not be included in labeling and packaging?
False or misleading information, indication and efficacy which is not approved, and usage and administration or expiration information that may cause risk under health and hygiene considerations.
17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?
Under the PMD Act, false or exaggerated advertisements and any advertisement before obtaining marketing authorization are prohibited. There are rules and guidelines relating to advertisements issued by the healthcare authority, as well as promotion codes or other self-imposed rules by industry associations.
18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?
Medicines and devices are only sold at hospitals, clinics and pharmacies and only delivered by licensed organization. Medicines can be posted, to reduce waiting time at pharmacy, if a pharmacist has given face to face medication instruction to the patient before dispensing and posting such medicine.
19. What are the restrictions and requirements for electronic marketing and advertising via email, by Internet, social media, and other channels?
There is no specific restrictions and requirements for electronic marketing and advertisement for prescription medicine and medical device. Therefore, the general legal framework applicable to advertisements of medicine and medical devices, and general electronic marketing and advertisement rules apply.
20. May medicines and devices be advertised or sold directly to consumers?
Not for prescription medicine and medical devices.
21. How is compliance monitored?
Generally, MHLW (Compliance and Narcotics Division) and each Prefecture government are in charge of compliance monitoring. In addition to such general monitoring, MHLW has introduced special monitoring activities for the advertisement of medicine (including oral promotion by sales reps) from 2017, and publishes a report every year.
22. What are the potential penalties for noncompliance?
Under PMD Act, potential penalties are up to two years imprisonment or up to two million yen fine, or both. A two million yen fine may also be applicable to a company.