Q.01

What is a quasi-drug in Japan?

In Japan, a quasi-drug (医薬部外品, iyaku-bugaihin) is a product defined in Article 2(2) of the PMD Act (the Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, etc.) as something whose action on the human body is mild (人体に対する作用が緩和なもの) and that falls into one of three groups set out in the Act [1]. It sits between a pharmaceutical and a cosmetic.

The three groups in Article 2(2) (my translation of the Japanese text):

  1. Items used for these purposes that are not machines or instruments (機械器具等):
    • (イ) preventing nausea or other discomfort, or bad breath or body odour;
    • (ロ) preventing prickly heat (あせも), skin soreness or chafing (ただれ) and similar conditions;
    • (ハ) preventing hair loss, promoting hair growth, or removing hair.
  2. Items used to control rats, flies, mosquitoes, fleas and similar organisms for the health of humans or animals, also not machines or instruments.
  3. Items designated by the Minister of Health, Labour and Welfare (厚生労働大臣が指定するもの) from among products used for drug purposes, meaning those in Article 2(1)(ii) or (iii) of the Act.

Groups 1 and 2 leave out any product that also has a drug purpose. The drug purposes in Article 2(1)(ii) and (iii) are:

  • diagnosing, treating or preventing disease in humans or animals;
  • affecting the structure or function of the human or animal body.

Such a product is a pharmaceutical unless the Minister designates it under group 3 [1].

How it fits with the other categories in the same Article:

  • Pharmaceuticals: the definition of "pharmaceutical" in Article 2(1) expressly excludes quasi-drugs [1].
  • Cosmetics: Article 2(3) defines cosmetics as mild-acting products applied to the body to clean or beautify it, make it more attractive, change its appearance, or keep skin and hair healthy. It also excludes quasi-drugs and anything that has a drug purpose as well [1].
  • Shared rules: the Act's term "manufacturing and marketing" (製造販売), defined in Article 2(13), covers quasi-drugs alongside drugs, cosmetics, medical devices and regenerative medicine products [1]. The Enforcement Order also treats quasi-drugs separately in its rules on marketing approval applications, for example Article 26 [2].

Approach: I read the official Japanese text of the PMD Act and its Enforcement Order as published by MHLW. I didn't look up the list of product types the Minister has designated under group 3, which sits in separate MHLW notifications.

Q.02

How do quasi-drug ingredient standards affect product approval?

Answer: The Japanese Standards of Quasi-drug Ingredients (医薬部外品原料規格, "外原規" or JSQI) are the reference specifications MHLW's product-category approval standards point to. If every ingredient meets a listed compendial specification and stays within the listed limits, you can follow a shortened, precedent-based review: you name the compendium and skip submitting the specification text, and often the efficacy and safety data for the active ingredient. If you go outside those limits, the review has to rest on your own specifications and data.

1. The legal frame (PMD Act)

  • Article 14(1): anyone who wants to manufacture and market a quasi-drug "must" (受けなければならない) obtain the Minister's approval for each product. The exception is quasi-drugs the Minister designates by setting standards [3].
  • Article 14(2)(iii): approval is refused if, after reviewing the product's name, ingredients, quantities, efficacy and so on, the product is found to lack the claimed effect or to have harmful effects out of proportion to that effect [3].
  • Article 14(5): the review includes checking whether the product is the same as already-approved products in ingredients, quantities, efficacy and similar points. This is the legal basis for precedent-based review [3].
  • Article 42(2): the Minister "may" set standards on the properties, quality and performance of quasi-drugs where needed to prevent harm to health [4].
    • A change plan cannot cover a change that would breach such a standard (Article 14-7-2(1)(ii)) [5].
    • Label items required by such a standard must appear on the immediate container (Article 59(xi)) [6].
    • The JSQI itself was issued by Director-General notification. None of the texts I read say whether it is an Article 42 standard.

2. How the ingredient standards plug into the category approval standards

  • Hair dyes: each active ingredient must meet the specification in the compendium its code points to. Code "Q" means the JSQI, "P" the Japanese Pharmacopoeia, "F" the Japan's Specifications and Standards for Food Additives, and "J" the JIS. A hair dye that does not fit the standard is instead reviewed on data you submit on efficacy, safety and the reasons for each ingredient [7].
  • Same coding in other standards: the standards for medicated toothpastes [8], bath preparations [9] and medicated soaps [10] use it too.
  • Permanent wave products: the standard also uses the JSQI's general test methods (for example the viscosity method) and its reagents within the product's own test methods [11].
  • Medicated shampoos and rinses (2014 notice):
    • Active ingredients "shall conform" to the JSQI 2006 specifications.
    • Additives must follow the Quasi-drug Additives List.
    • Products outside the notice need either documents showing approval precedent or efficacy and safety data [12].
  • Medicated cosmetics (2008 active-ingredient list): the list gives precedent specifications and concentration ranges; code 51 means JSQI 2006. If the product matches approved products in efficacy, dosage and form, and stays within the list, efficacy and safety data on the active ingredient are "in principle" not required [13].
  • Excipients: the MHLW Quasi-drug Additives List has 2,746 numbered entries, for example glycerin at no. 689 [14]. The 2022 Hair Dye Additives List revision maps each additive to its JSQI 2021 name, alongside the older names [15].

3. What it changes in the application form (medicated soap guidance, 2018)

  • Ingredient names must be the names used in the relevant compendium.
  • For ingredients on the notice's tables or the Additives List, the specification can be cited in short form (日局, 食添, 局外規, 外原規). The specification text itself is then left out of the application (添付を省略すること).
  • Premixes go under a "separate specification" (別紙規格) heading that lists each component's specification, or are broken down into their components.
  • Fragrances above 1% need their specification attached.
  • Quantities outside the notice's values take the product outside the notice.
  • Measured results for the product's own specifications and test methods (in principle 3 lots × 3 runs) must still be attached [16].
  • The same short-form rules appear in the toothpaste, bath preparation, hair dye and permanent wave application guidance [17][18][19][20].

4. What a JSQI monograph sets Taking dipotassium glycyrrhizinate in JSQI 2021 as an example, the monograph sets:

  • assay content of 96.0-102.0% on the dehydrated basis;
  • appearance and identification tests;
  • pH 5.0-6.0;
  • heavy metals at 10 ppm or less and arsenic at 4 ppm or less;
  • water at 8.0% or less [21].

Citing "外原規" for an ingredient therefore commits the product to that full specification.

Practical takeaway: the JSQI and the other compendia decide whether an ingredient's quality is already "known." Sticking to listed specifications, listed additives and precedent concentrations keeps you on the shortened precedent route. A new ingredient, a non-compendial grade or a level above the limits sends you to a full review on your own specifications and data. Some notices, like the 2014 shampoo and rinse notice and the 2008 medicated-cosmetics list, still cite JSQI 2006, while newer ones cite JSQI 2021. The documents I read don't say how the older citations map onto the 2021 edition.

Approach: I read the PMD Act, MHLW's quasi-drug approval standards and application guidance for each product category, the JSQI 2021 monographs and the Quasi-drug Additives List. The PMDA quasi-drug review reports I found didn't discuss ingredient standards.

Q.03