The regulatory framework for pharmaceuticals in Japan, governed by the Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices (PMD Act or Yakkiho), establishes distinct categories and stringent controls for medications, particularly those requiring a prescription. Understanding the classification of prescription pharmaceuticals (shohōsen iyakuhin), their differentiation from other medical-use drugs (iryō-yō iyakuhin), and the detailed regulations governing their sale is crucial for any entity involved in the Japanese pharmaceutical market. This system prioritizes patient safety by ensuring that potent medications are used under appropriate medical supervision.

The Foundation: "Medical-Use Pharmaceuticals" (医療用医薬品 - Iryō-yō Iyakuhin)

Before delving into the specifics of "prescription pharmaceuticals," it is important to understand the broader category of "medical-use pharmaceuticals" (iryō-yō iyakuhin). These are pharmaceuticals intended for use by healthcare professionals (physicians, dentists, etc.) in the diagnosis, treatment, or prevention of diseases. They are distinct from Over-The-Counter (OTC) drugs, which can be purchased by consumers without a prescription for self-medication of minor ailments. Medical-use pharmaceuticals, due to their potency, potential for side effects, or the need for professional judgment in their application, are supplied through channels involving healthcare professionals and pharmacies. Within this broad category, a specific subset is designated as "prescription pharmaceuticals."

The Core Category: "Prescription Pharmaceuticals" (処方箋医薬品 - Shohōsen Iyakuhin)

Article 49, Paragraph 1 of the PMD Act forms the legal cornerstone for "prescription pharmaceuticals." It stipulates that pharmaceuticals designated by the Minister of Health, Labour and Welfare (MHLW) as requiring a prescription cannot be sold or supplied to anyone other than a person who has received a prescription from a physician, dentist, or veterinarian (in the case of drugs for animal use prescribed by veterinarians).

Designation Criteria

The MHLW designates pharmaceuticals as "prescription-only" based on specific criteria aimed at safeguarding public health. These criteria, detailed in notifications such as the MHLW Notification Yakushoku Hatsu No. 0210001 dated February 10, 2005, consider products that:

1. Require Professional Medical Judgment for Use: This includes pharmaceuticals where a physician's or dentist's diagnosis and the establishment of a treatment plan are essential. These drugs might be difficult to use correctly, prone to developing resistance (e.g., certain antibiotics), or necessitate careful selection based on an individual patient's condition, constitution, or comorbidities.
2. Carry a Risk of Serious Adverse Effects: If a pharmaceutical has the potential for severe side effects that necessitate regular medical examinations or monitoring by a healthcare professional to prevent or manage these risks, it is likely to be designated as prescription-only.
3. Possess a Potential for Misuse or Dependence: Pharmaceuticals with properties such as stimulant effects, a risk of dependence, or a potential for abuse if not used under strict medical supervision are also prime candidates for prescription status.

Certain categories of medical-use pharmaceuticals are almost invariably designated as prescription-only due to their inherent risks or specialized nature. These typically include:

• Radioactive pharmaceuticals
• Narcotics
• Psychotropic drugs
• Stimulants and their raw materials
• Specified biological products (e.g., blood products, vaccines with particular safety considerations)
• Injectable preparations

It is important to note that in-vitro diagnostics, even if used in a medical setting, are generally not classified as prescription pharmaceuticals under this framework.

Strict Sales Regulations for Prescription Pharmaceuticals

The default rule under PMD Act Article 49, Paragraph 1 is unequivocal: the sale or supply of designated prescription pharmaceuticals is prohibited unless it is to an individual presenting a valid prescription from an authorized prescriber (physician, dentist, or veterinarian).

The Role of Pharmacists and Pharmacies (Yakkyoku)

Pharmacies (yakkyoku) and pharmacists (yakuzaishi) are central to the dispensing process. When a patient presents a prescription:

• Pharmacists are responsible for verifying the legality and appropriateness of the prescription.
• They must dispense the medication in accordance with the prescription and provide necessary counseling to the patient on its correct usage, potential side effects, and storage (a duty reinforced by the Pharmacists Act, Article 25-2, requiring provision of information and guidance based on pharmaceutical knowledge).
• The 2019 amendments to the PMD Act, effective September 2020, also laid the groundwork for permanent provisions regarding online medication guidance (onrain fukuyaku shidō), allowing pharmacists to provide counseling remotely under specific conditions, further evolving how prescription medications are dispensed and managed.

Record-Keeping Obligations

Pharmacies are required to maintain detailed records of dispensed prescriptions for a specified period (typically three years from the date of dispensing). These records must include information such as the patient's name, the name and quantity of the drug dispensed, the date of dispensing, and details of the prescribing physician and pharmacy.

Exceptions to the Prescription Requirement: "Legitimate Reasons" (Seitō na Riyū)

While the prescription requirement is stringent, PMD Act Article 49, Paragraph 2 acknowledges that there can be "legitimate reasons" (seitō na riyū) for selling or supplying prescription pharmaceuticals without a prescription. The MHLW has provided detailed guidance on what constitutes such legitimate reasons, primarily through notifications like Yakushoku Hatsu No. 0318004, dated March 18, 2014. These exceptions are narrowly defined and are generally applicable in specific, often emergency or public health-related, situations:

1. Large-Scale Disasters: In situations where obtaining a physician's consultation or a prescription is difficult due to a major disaster, pharmacies may supply necessary prescription drugs to patients or their caregivers.
2. Stockpiling by Local Governments: Sales to local government bodies for the purpose of emergency stockpiling of essential medicines.
3. Municipal Vaccination Programs: Supply of vaccines (which are prescription pharmaceuticals) to municipalities for public vaccination initiatives.
4. Emergency Aid by Midwives: Sales to licensed midwifery clinics for necessary emergency first aid that midwives are legally permitted to provide.
5. Emergency Life-Saving by Paramedics: Supply of specific prescription drugs to fire departments or emergency medical services for use by certified paramedics performing emergency life-saving procedures.
6. Shipboard Medicine Chests: Sales to ship owners for equipping vessels with necessary medicines, based on a certificate issued by the ship's captain, in accordance with the Mariners Act.
7. Educational and Research Purposes: Supply to universities, research institutions, or other recognized educational bodies for legitimate educational or scientific research purposes.
8. Treatment at Diplomatic Missions Abroad: Supplying prescription pharmaceuticals to staff of Japanese diplomatic missions overseas based on a diagnosis by a physician practicing at that mission, for the treatment of the staff or their dependents.
9. Organ Transplantation Activities: Sales to authorized organ procurement organizations for use in activities related to organ transplantation.
10. Official Testing and Inspection: Supply to designated testing or inspection institutions for use in official quality control or analytical testing.
11. Use as Raw Materials: Sales to licensed manufacturers who will use the prescription pharmaceutical as a raw material in the production of other pharmaceuticals, quasi-drugs, cosmetics, or medical devices.
12. Veterinary Use (Human Pharmaceuticals): In cases where a human-use prescription pharmaceutical is necessary for the treatment of an animal, it may be supplied based on the direct instruction (not necessarily a formal prescription in all cases, depending on the specific veterinary context and drug) of a veterinarian.

Even when these exceptions apply, pharmacies are typically expected to exercise due diligence, such as confirming the identity and authority of the recipient, providing necessary information about the drug, limiting quantities to what is genuinely needed for the situation, and maintaining thorough records of the transaction. Wherever possible, instructions or confirmations from a physician or relevant authority are encouraged.

"Medical-Use Pharmaceuticals Other Than Prescription Pharmaceuticals"

Beyond the formally designated "prescription pharmaceuticals," there exists a category of "medical-use pharmaceuticals other than prescription pharmaceuticals" (shohōsen iyakuhin igai no iryō-yō iyakuhin). These are ethical drugs that, while intended for professional use, have not been specifically designated by the MHLW as requiring a prescription for every sale.

Legally, these pharmaceuticals could be sold by a pharmacy without a prescription. However, the MHLW, through guidance (such as the aforementioned Yakushoku Hatsu No. 0318004), strongly advises that pharmacies treat these drugs with a level of caution similar to that applied to designated prescription pharmaceuticals. This is because they are still potent medical-use drugs, and their unsupervised use could pose risks.

The prevailing guidance recommends that pharmacies selling such drugs without a prescription should do so only under limited and justifiable circumstances, such as:

• When OTC alternatives have been considered and are deemed unsuitable or unavailable.
• Strongly recommending that the patient consult a physician.
• Limiting the quantity sold, typically to the smallest original pack size or a quantity sufficient for a very short duration of use.
• Creating and maintaining detailed sales records, including the patient's details, the drug sold, quantity, and date.
• Ensuring that a pharmacist is directly involved in the sale, providing counseling, and, where possible, checking the patient’s medication history (e.g., through a medication record book - okusuri techō) to prevent adverse interactions or therapeutic duplication.

In practice, most pharmacies in Japan are very conservative in selling these "medical-use pharmaceuticals other than prescription pharmaceuticals" without a prescription. The professional ethos and the emphasis on patient safety mean that pharmacists will usually err on the side of caution and refer the patient to a physician.

Regulation of Advertising for Prescription Pharmaceuticals

The advertising of prescription pharmaceuticals in Japan is strictly controlled. The primary principle is that direct-to-consumer advertising (DTCA) for prescription drugs is generally prohibited. Advertising and promotional activities are predominantly directed towards healthcare professionals (physicians, dentists, pharmacists).

These restrictions are enforced through several articles in the PMD Act:

• Article 66: Prohibits false or exaggerated advertising concerning the name, manufacturing method, efficacy, effects, or performance of pharmaceuticals, quasi-drugs, cosmetics, medical devices, or regenerative medicine products. This applies to all forms of advertising, including labeling and package inserts.
• Article 67: Contains provisions regarding advertising that could be misleading about a physician's or other professional's endorsement.
• Article 68: Prohibits the advertising of pharmaceuticals, medical devices, or regenerative medicine products before they have received marketing approval, and also prohibits advertising for unapproved indications (off-label uses).

In addition to the PMD Act itself, detailed guidelines such as the "Standards for Appropriate Advertising of Pharmaceuticals, etc." (医薬品等適正広告基準 - Iyakuhin-tō Tekisei Kōkoku Kijun) provide specific do's and don'ts for pharmaceutical advertising. These standards cover aspects like the type of information that can be presented, comparisons with other products, and the overall tone and balance of promotional materials. Enforcement is carried out by the MHLW and prefectural governments, and violations can lead to administrative sanctions or penalties.

The Crucial Role of the Marketing Authorization Holder (MAH)

The Marketing Authorization Holder (seizō hanbai gyōsha) plays a central and legally mandated role in the lifecycle of all pharmaceuticals, including prescription drugs. The MAH is the entity responsible for:

• Obtaining marketing approval for the pharmaceutical product from the MHLW.
• Ensuring the product's quality, efficacy, and safety in the Japanese market. This includes adherence to Good Quality Practice (GQP) for product release and Good Vigilance Practice (GVP) for post-marketing safety surveillance.
• Accurately labeling the product, including clearly indicating on the package and package insert if it is a "prescription pharmaceutical" (処方箋医薬品).
• Providing comprehensive and accurate product information to healthcare professionals. This includes creating and updating package inserts and other informational materials.
• Managing any post-marketing safety issues, including conducting recalls if necessary.

Foreign manufacturers wishing to sell prescription pharmaceuticals in Japan must either appoint a licensed MAH based in Japan to act on their behalf or establish their own Japanese entity and obtain an MAH license.

Recent Developments and Future Considerations

The regulatory landscape for prescription pharmaceuticals is not static. Recent PMD Act amendments and evolving practices continue to shape how these drugs are managed:

• Emergency Approval System: The 2022 amendments introduced an emergency approval system (PMD Act, Article 14-3). Pharmaceuticals approved under this expedited pathway during public health emergencies will typically be prescription pharmaceuticals, subject to specific post-approval data collection and safety monitoring requirements.
• Online Healthcare and Dispensing: The aforementioned permanent establishment of online medication guidance, coupled with developments in telemedicine, is gradually changing how patients access medical consultations and receive prescription medications, though physical dispensing from a pharmacy (or delivery from one) remains the norm.
• Emphasis on Pharmacist Intervention: There is a continuous push to enhance the role of pharmacists in medication therapy management, including for prescription drugs, focusing on optimizing therapeutic outcomes and minimizing risks through patient counseling and collaboration with physicians.

Conclusion

Japan's regulatory system for prescription pharmaceuticals is characterized by a strong emphasis on physician oversight and pharmacist involvement to ensure patient safety. The clear designation of "prescription pharmaceuticals" under the PMD Act, coupled with stringent sales regulations, limited exceptions to the prescription requirement, and tight controls on advertising, creates a well-defined framework. For pharmaceutical businesses, a thorough understanding of these classifications, the criteria for designation, the rules governing sales and promotion, and the overarching responsibilities of the Marketing Authorization Holder is fundamental to compliant and successful operations in the Japanese market. The system is designed to balance the need for patient access to necessary medicines with robust safeguards against their misuse or inappropriate use.