Standards for Marketing Approval of Antihemorrhoids (External Preparations) in Japan

Standards for Marketing Approval of Antihemorrhoids (External Preparations) (Japan)

The Standards for Marketing Approval of Antihemorrhoids (External Preparations) were issued by Japan’s Pharmaceuticals and Medical Devices Agency as Notification PFSB No.277 on March 22, 1995. These standards set out the regulatory criteria for medicines intended for relief of hemorrhoidal symptoms in the anus and rectum. Preparations that deviate from these standards must be justified with efficacy and safety data. (PMDA, 000272500.pdf).

Scope

Antihemorrhoid external preparations cover medicines formulated to relieve pain, itching, swelling, bleeding and erosion associated with hemorrhoids. Traditional Kampo formulas and crude drug remedies consisting only of crude drug are not covered by these standards. (PMDA, 000272500.pdf).

Types of Active Ingredients

• Permissible active ingredients are listed in Table 1, grouped by columns with specific combination rules.
• Preparations must include at least one active ingredient from Column I of Table 1.
• Active ingredients from different columns may be combined, with limits such as only one ingredient from Columns II, III, V or VI per preparation.
• Certain combinations within columns (e.g., dibucaine hydrochloride with dibucaine) and specific pairs in Column VII are not allowed. (PMDA, 000272500.pdf).

Quantities of Active Ingredients

• Maximum concentrations for each active ingredient appear in the “A” column for ointments and external liquids and the “B” column for applicator ointments and suppositories.
• Minimum concentrations or single doses are defined as fractions of the respective maximums, with special conditions when Column I ingredients are included.
• Specific fractional limits apply to Group 2 ingredients in Columns VII and IX.
• When two Column I Group 1 ingredients are combined, the sum of fractional concentrations (relative to their maximums) must not exceed 1. (PMDA, 000272500.pdf).

Dosage Forms

Approved dosage forms include suppositories (including soft capsules), ointments, and external liquids (including aerosols). (PMDA, 000272500.pdf).

Dosage and Administration

• Ointments to be applied by rubbing and external liquids should be applied to the anal area up to three times a day; instructions must be clearly indicated.
• Applicator ointments and suppositories are applied one dose at a time, up to three times a day; applicator methods must be clearly described.
• Children younger than 7 years are not approved; for ages 7 to under 15, the maximum single dose is half of the standard maximum from Table 1. (PMDA, 000272500.pdf).

Indications

Indications are limited to relief of pain, itching, swelling, bleeding and erosion associated with hemorrhoids, and disinfection for ointments applied by rubbing and external liquids.

• Itching requires ingredients from specified groups (e.g., Group 1 of Column I, III or VI),
• Swelling and bleeding require ingredients from Columns II, III or IV,
• Erosion requires ingredients from Column IV,
• Disinfection requires Group 1 of Column V. (PMDA, 000272500.pdf).

Summary

These standards form the regulatory framework for marketing approval of external antihemorrhoid medicines in Japan. Conformance with active ingredient types, concentration limits, dosage forms, dosing instructions and indications is essential for approval. (PMDA, 000272500.pdf).