China Instructions for Toothpaste Notification Dossiers Require Mandatory Efficacy Evaluation and Safety Assessment

On Jan. 6, 2021, China National Medical Products Administration (NMPA) released the draft Instructions for Toothpaste Notification Dossiers for public consultation ^[1]. Any suggestions can be mailed to ChemLinked ([email protected]) prior to Jan. 27, 2021, and we'll submit them to the NMPA.

Background

According to the Cosmetic Supervision and Administration Regulation (CSAR), toothpaste shall be regulated in accordance with the regulations on general cosmetics, requiring notification, testing, safety assessment, efficacy evaluation, new toothpaste ingredient application, etc. The toothpaste notifier shall report the manufacture, import, and adverse reaction monitoring of notified toothpaste to the competent authority annually.

Instructions for Toothpaste Notification Dossiers are drafted to standardize the toothpaste notification dossiers in China. The contents include:

General Rules
Requirements for User Information Related Dossiers
Requirements for Notification Dossiers
Requirements for Notification Information Changes
Requirements for Notification Cancellation
Supplementary Rules

Documents Necessary for Toothpaste Notification

Account Application

1. Notifier information form and the resume of the person in charge of quality and safety;

2. Overview of the quality management system of the notifier;

3. Overview of the adverse reaction monitoring and evaluation system of the notifier;

4. Domestic responsible person information form (for overseas notifier);

5. The original copy of the authorization letter of the domestic responsible person and the original notarization (for overseas notifier);

6. Manufacturer information form and resume of the person in charge of quality and safety;

7. The original copy of the GMP certification documents (for the overseas manufacturer).

Toothpaste Notification

1. Toothpaste notification information form and related documents

Product name
Product classification
Entrusted manufacture confirmation (require entrusted manufacture relationship document for imported toothpaste)
Certificate of Free Sales (for imported toothpaste whose product sales packaging is specially designed for the Chinese market, also require explanatory documents stating that the product formula and production process are consistent with the product in the country of origin)
Explanatory documents for formula design according to the consumption needs of Chinese consumers (for imported toothpaste whose product formula is specially designed for the Chinese market)
Letter of commitment to undertake product quality and safety responsibility (if other enterprises or institutions indicate "joint research and development," "produced by," or "supervised by" on the product label);

2. The naming basis of the product name;

3. Product formula;

4. Product executive standards;

5. Product label sample;

6. Product testing report;

7. Product safety assessment documents.

Toothpaste ingredient manufacturers shall submit ingredient quality and safety related information through the ingredient safety information service platform of the NMPA. The ingredient submission code will be automatically generated after the submission of quality and safety information. The toothpaste notifier can fill in the ingredient submission code when conducting notification.

Toothpaste Efficacy

1) Toothpaste Classification

Toothpaste is classified according to efficacy and target users and adopts a coding system. The classification code is composed of 2 layers of numbers, and each layer is separated by "-" and represented by a 2-digit number. The details of the coding rules are as follows.

Layer	Code	Category
Efficacies	01	Basic cleansing
	02	Caries prevention
	03	Inhibition of dental plaque
	04	Anti-dentin hypersensitivity
	05	Reduce gum problems
	06	Whitening
	07	Anti-dental calculus
	08	Reduce bad breath
	09	Other efficacies

Target Users	01	Adult
Target Users	02	Children (6 months to 12 years old)

For example:

The classification code of adult whitening toothpaste is 06-01;
The classification code of cleansing and caries prevention toothpaste for children is 0102-02.

2) Permitted Efficacy Claims

Toothpaste shall not claim the efficacy beyond the scope specified in the following table.

Category	Scope of Permitted Efficacy Claims
Basic cleansing	Clean teeth/clean mouth, maintain oral hygiene, maintain oral health, reduce soft dirt, freshen breath, refreshing taste
Caries prevention	Prevent dental caries, strengthen teeth, prevent cavities, inhibit teeth demineralization, promote teeth remineralization
Inhibition of dental plaque	Inhibit dental plaque and reduce the formation of dental plaque
Anti-dentin hypersensitivity	Anti-dentin sensitivity, reduce the irritation of hot and sour on the teeth, reduce the irritation caused by hot and sour, alleviate sensitivity, anti-sensitivity, soothing, repair sensitive teeth, seal dentin tubules
Alleviating gum problems	Clear fire, dispel fire, improve gum health, protect gums
Whitening	Whiten teeth, whiten teeth through oxidation reaction, reduce exogenous staining, mechanically reduce exogenous staining, chemically reduce exogenous staining, achieve whitening effects through optical effects
Anti-dental calculus	Reduce dental calculus, decompose dental calculus, reduce dental calculus formation, prevent dental calculus, inhibit dental calculus formation
Alleviating bad breath	Reduce bad breath, reduce bad odor, remove volatile sulfur compounds, inhibit bad breath-causing bacteria
Other efficacies	Moisturize the mouth, improve dry mouth
Note: Children's toothpaste can only claim cleansing and caries prevention efficacy.

The permitted efficacy claims in the above table are fixed combinations and shall not be added, deleted, or adjusted at will. If the above claims are used in conjunction with other words, it shall comply with Administrative Measures on Toothpaste and Administrative Measures on Cosmetics Labeling.

3) Efficacy Evaluation

Efficacy evaluation is mandatory for all toothpaste except for cleansing toothpaste. The toothpaste notifier shall submit efficacy evaluation abstracts when conducting notification and keep the efficacy evaluation report for future reference. The efficacy evaluation abstracts should include the efficacy evaluation items, evaluation methods, evaluation institutions, conclusion, etc.

Efficacy evaluation should be carried out based on qualitative or quantitative testing of functional ingredients in the toothpaste. Efficacy evaluation is divided into 1) clinical evaluation and 2) laboratory evaluation.

Before conducting clinical evaluation, the product's microbiological, physical and chemical, and special safety tests should be completed, and a written report should be issued. Microbiological and physical and chemical tests shall be conducted by testing institutions that have obtained China Inspection Body and Laboratory Mandatory Approval (CMA) and have corresponding testing capabilities.

Toothpaste Categories	Efficacy Evaluation Methods	Efficacy Evaluation Institution Qualifications
Claim the efficacies of caries prevention, inhibition of dental plaque, anti-dentin hypersensitivity, and alleviating gum problems	Adopt clinical evaluation methods in accordance with the requirements of Administrative Measures on Toothpaste, national standards, industry standards, and technical specifications	1. Class A tertiary oral medical institution with the drugs or medical devices clinical trial bases qualifications recognized by the national regulatory agency; or 2. Stomatological hospital awarded the National Key Clinical Specialty (Stomatology) by the health supervision and administration department of the State Council; or 3. Provincial dental specialist hospital with qualifications for clinical trial bases for drugs or medical devices. Laboratory evaluation reports can be issued by testing institutions that have been filed with the NMPA*.
Claim the efficacies of whitening, anti-dental calculus, alleviating bad breath, and improving oral problems	Methods stipulated by domestic and foreign laws, regulations, technical standards, and technical specifications; or Methods published on guidelines from authoritative organizations or technical institutions and industry associations, professional academic journals, etc. If a method developed by the laboratory is used, the method should be confirmed in accordance with the CMA/CNAS method confirmation process, and the complete text of the self-developed method should be included in the evaluation report.
Quantitative efficacy claims (such as efficacy retention time, statistical data, degree, etc.)	Carry out efficacy evaluation according to regulations.

Efficacy Evaluation Exemption

Toothpaste that uses fluoride as a caries prevention ingredient, and meets the fluoride content required by national standards and technical specifications, can be exempt from clinical evaluation of caries prevention efficacy.
The efficacy evaluation is not required for the product of the same notifier, claiming the same efficacy, using the same functional ingredients, and the addition amount is not less than the toothpaste that has been evaluated. But the efficacy of the functional ingredient needs to be stated in the efficacy evaluation abstracts.

Safety Assessment

Toothpaste notifier shall carry out product safety assessment in accordance with the Technical Guidelines for Cosmetic Safety Assessment and submit a product safety assessment report when conducting notification.

For the first use of food additives or food ingredients (have national standards) in toothpaste, the ingredient use frequency and exposure in toothpaste should be compared with the corresponding indicators when used in food, and a safety assessment report should be submitted.

Required Information on Labels

Toothpaste labeling requirements must comply with Administrative Measures on Toothpaste and Administrative Measures on Cosmetics Labeling. The following is the required information on toothpaste labels.

1. Product name

2. Name and address of the notifier (name and address of the domestic responsible person for imported toothpaste)

3. Name and address of the manufacturer (require production license number for domestic cosmetics)

4. Product executive standard number

5. List of ingredients

6. Net content

7. Durability

8. Application method

9. Safety warnings

10. Other content prescribed by laws, administrative regulations, and mandatory national standards

Future Toothpaste Regulations and Standards

China Oral Care Industry Association (COCIA) Main Work Plan for 2021 was released on Jan. 6, which revealed the toothpaste regulations and standards that will be introduced in the future ^[2].

Establish a toothpaste, mouthwash, ingredient toxicology database;
Determine the qualification requirements for toothpaste safety assessment institutions;
Establish a list of toothpaste safety assessment and efficacy evaluation institutions;
Improve the toothpaste efficacy evaluation standard system.

Earlier on Jul. 29, 2020, COCIA authorized by the NMPA collected existing toothpaste ingredients in the Chinese market from companies ^[3]. Inventory of Existing Toothpaste Ingredients is being formulated and will be released in the future.

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