Japan Revises Quasi-drug Ingredient Standards and Licensing Requirements

Japan has amended 15 general testing methods and updated specifications for 222 quasi-drug ingredients under the Japanese Standards of Quasi-drug Ingredients 2021 (JSQI 2021). Additionally, the application requirements for manufacturing and sales licenses have been revised to align with these changes.

On March 21, 2025, Japan Ministry of Health, Labour and Welfare (MHLW) issued notification announcing significant amendments to the Japanese Standards of Quasi-drug Ingredients 2021 (JSQI 2021). JSQI 2021 is the foundational technical standard for quasi-drug ingredients, outlining the basic specifications and testing methods required for regulatory compliance.

This revision introduces several updates to both general testing methods and ingredient specifications, aiming to enhance quality control and regulatory consistency. The changes came into effect immediately upon publication, but a transition period will be in place until September 30, 2026, allowing companies to continue applying the previous standards during this time.

Key Revisions to JSQI 2021

1. Updates to General Testing Methods

A major update includes the addition of the 2,2'-bipyridyl colorimetric method to "48 Iron Test Method". Additionally, 14 other general testing methods have been revised to align with the Japanese Pharmacopoeia and other official regulatory standards.

No.	Revised Testing Method	No.	Revised Testing Method
1	2. Acrylonitrile test method	2	6. Anionic surfactants quantitative method
3	9. Ester value determination method	4	27. Perfume test method
5	40. Water-soluble collagen test method	6	47. Qualitative reaction
7	48. Iron test method	8	61. Non-saponifiable matter assay method
9	69. Methanol test method	10	75. Lipase titer test method
11	76. Sulfate test method	12	80. Standards
13	81. Reagents and test solutions	14	82. Standard solutions for volumetric analysis
15	83. Standard solutions

2. Revised Specifications for 222 Ingredients

No.	Examples of the Revised Ingredients
1	Acrylamide•Acrylate•Methoxypolyethylene Glycol Methacrylate Copolymer
2	2-Acrylamido-2-methylpropanesulfonic Acid•Methacryl Acid N,NDimethylaminoethyl Copolymer
3	Acrylic Acid•Alkyl Methacrylate Copolymer
4	Astaxanthin Solution
5	Potassium L-Aspartate
6	Magnesium L-Aspartate
7	N-Acetyl Glucosamine
8	N-Acetyl-L-Cysteine
9	5-Amino-o-cresol
10	2-Amino-4-nitrophenol
11	2-Amino-5-nitrophenol
12	1-Amino-4-methylaminoanthraquinone
13	2-Amino-2-Methyl-1-Propanol
14	Sodium Bisulfite
15	Alcaligenes Polysaccharides
16	Sodium Alkanesulfonate
17	Ammonium Alkyl (12,14,16) Sulfate
18	Propyleneglycol Alginate
19	Aluminium Powder
20	Alkyl (C12–C15) Benzoate
21	Benzyl Benzoate
22	Umber
23	Propylene Glycol Isostearate
24	Isostearoyl Hydrolyzed Collagen (1)
25	Inositol
26	3,3′-Iminodiphenol
27	Bovine Plasma Extract
28	Undecylenic Acid Monoethanolamide
29	Titanated Mica
30	Estradiol
Notes: For the complete list of the 222 revised ingredients, please refer to the MHLW notification issued on March 21, 2025. ¹

Changes to Manufacturing and Sales License Application Requirements

Along with the revisions to JSQI 2021, the MHLW has also updated the regulatory requirements for quasi-drug manufacturing and sales license applications.

An example of the application formFrom March 21, 2025, all new quasi-drug approval applications shall comply with the updated standards if they contain the revised ingredients. Applicants can simply cite "Revised Japanese Standards of Quasi-Drug Ingredients" (“改正外原規” in Japanese)" in the "Ingredient and Content" column of the application form, without needing to provide detailed specifications. However, companies have the option to continue using the pre-revised standards until September 30, 2026.

For existing products that have already been approved and contain the revised ingredients, companies may still use the previous standards until September 30, 2026, but must adhere to the updated standards starting October 1, 2026. If they wish to continue with the old standards beyond this date, they must submit a minor change notice by the end of September 2026. This notice should specify that the application is based on Notification 0321 No. 1, issued by the MHLW, regarding the partial amendments to JSQI 2021.

In addition, for products that include revised JSQI testing methods in the "Specifications and Testing Methods" section, the previous JSQI 2021 testing methods will remain valid until September 30, 2026. From October 1, 2026, the revised JSQI 2021 testing methods must be used.

The MHLW also clarified that if there are changes to reagent or solution names due to the recent JSQI revision, companies will not need to submit a separate change application. These name changes can be incorporated into the next minor change notice or partial change application for other reasons, streamlining the regulatory process.