Standards for Marketing Approval of Over-the-Counter Drugs in Japan

1. Background and Policy Intent The standards for marketing approval of over-the-counter (OTC) drugs in Japan were established to standardize the approval process for combination drugs in various categories. These standards ensure the safety, efficacy, and appropriate usage of OTC products through specified active ingredients, dosages, forms, and indications. Non-conforming preparations require submission of efficacy and safety data along with justification for review. The policy aims to facilitate consistent regulatory decisions while excluding most Kampo medicine formulas unless specified. Source: https://www.pmda.go.jp/files/000272504.pdf The document provides English translations of these standards, issued by the Ministry of Health, Labour and Welfare, with notifications dating from 1986 to 2015.
2. Target Products and Eligibility Types The standards apply to oral OTC drugs for symptom relief in specific categories:

Cold remedies (e.g., for runny nose, cough) Antipyretic analgesics (e.g., for headache, fever) Antitussives and expectorants (e.g., for cough, sputum) Oral remedies for rhinitis (e.g., sneezing, stuffy nose) Gastrointestinal medicines (e.g., hyperacidity, indigestion) Laxatives (e.g., constipation) Antivertigo medicines (e.g., motion sickness) Ophthalmic medicines (e.g., eye inflammation) Vitamin preparations (e.g., supplements) Other categories like enemas, anthelmintics, nasal drops, antihemorrhoid preparations, athlete’s foot remedies, and dermatologicals

Eligibility requires products to include active ingredients from designated tables, with combinations limited by groups or columns to avoid prohibited pairings. Source: https://www.pmda.go.jp/files/000272504.pdf 3. Consultation Pathway Before Approval For preparations that do not conform to the standards, applicants must submit data on efficacy, safety, and justification for the combination, implying a need for pre-approval consultation or review with authorities to assess deviations from the norms. Source: https://www.pmda.go.jp/files/000272504.pdf No explicit consultation pathway is detailed beyond the requirement for additional data submission. 4. Approval Application and Review Expectations Applications must adhere to the standards outlined in tables for:

Active ingredients and quantities (e.g., maximum daily doses like 900 mg for acetaminophen) Dosage forms (e.g., tablets, syrups, excluding certain forms like elixirs) Administration schedules (e.g., 3 times per day) Indications tied to ingredients (e.g., relief of cold symptoms) Packaging limits (e.g., 2-day supply for syrups)

Review is based on compliance with these criteria. Age restrictions apply, such as no approval for children under 5 in certain forms. Non-standard products require submission of supporting data. Source: https://www.pmda.go.jp/files/000272504.pdf 5. Procedure After Approval (Post-Marketing Obligations) The document does not specify post-marketing obligations, focusing primarily on pre-approval standards. 6. Practical Considerations and Positioning Versus Other Pathways Practical considerations include:

Strict limits on ingredient combinations (e.g., sums of dose ratios ≤1, lower limits at 1/5th max dose) Child dosages calculated via coefficients in tables Prohibitions on certain pairings (e.g., no Ephedra with specific ingredients) Dosage forms and administration tailored to categories Indications precisely linked to approved ingredients

These standards position OTC combinations distinctly from Kampo or non-conforming reviews, where additional justification is needed. Vitamins can be added with mild effects and proper justification. Source: https://www.pmda.go.jp/files/000272504.pdf 7. Effective Date The standards stem from notifications issued between July 29, 1986 (ophthalmic medicines) and March 25, 2015 (cold remedies, antipyretics, etc.), with revisions up to May 15, 1998 (laxatives). The English version is as of October 2015. Source: https://www.pmda.go.jp/files/000272504.pdf