CSAR Subsidiary Regulations: China Modifies Requirements for New Cosmetic Ingredients Registration and Notification Dossiers

On Aug. 28, 2020, China National Institutes for Food and Drug Control (NIFDC) released the first draft Instructions for New Cosmetic Ingredient Registration and Notification Dossiers for public consultation ^[1]. The registration and notification dossiers of a natural or artificial ingredient that is applied in cosmetic products for the first time in China shall meet the requirements stipulated in the Instructions.

Based on the collected public opinions, National Medical Products Administration (NMPA) drafted and released the second edition of the Instructions on Nov. 5 ^[2]. Any suggestions can be mailed to ChemLinked ([email protected]) before Nov. 29, 2020, and we'll submit to the NMPA.

The following summarizes the key points of the second draft. The differences from the first draft have been marked in red.

*For the analysis of the first draft you can refer to CL News.

1. Registration and Notification Dossiers

1) Dossiers Necessary for Applying an Account in the NCI Registration and Notification Information System

Information form of registrant and notifier;
Overview of the adverse reaction monitoring and evaluation system;
For oversea registrant and notifier, the information form and the original power of attorney of the domestic responsible person (RP), and the original notarial certificate.

A power of attorney should include at least:

Names of the registrant, notifier and domestic responsible person

Clarification on who is the Agent (Attorney-in-fact) and Principal

The scope of authorization

Authorization period

Notes:

One NCI should not authorize multiple RPs;
The RP should carry out the registration/notification work within the authorization scope;
The RP should re-submit the extended power of attorney before the authorization period expires; otherwise, the RP cannot continue to carry out new registration or notification work.

2) Dossiers Necessary for NCI Registration/Notification

Dossiers categories required for NCI registration and notification

1.	Registration/Notification information form
2.	R&D report
3.	Research documents on the NCI preparation techniques, stability and quality control standards
4.	Safety assessment documents
5.	Functional basis combined with NCI application purpose
6.	Technical requirements (available for public)
7.	Other helpful documents
Note: In principle, NCI should not be a compound ingredient. If two or more components coexist inevitably due to production technology or process, etc., they should apply for registration or notification as one NCI, and provide relevant research documents that two or more components inevitably coexist. *For the detailed registration and notification dossiers requirements, please refer to ChemLinked coslist (will be updated soon).

Comparison of Various Ingredients Dossiers Requirements

Compared with low-risk NCI, additional toxicological tests dossiers are required for high-risk, relative high-risk NCI and ingredients that are used in cosmetics for the first time both in China and foreign countries.

New Ingredients	Supervision Mode	Special Requirements for Toxicological Tests
Ingredients that are used in cosmetics for the first time both in China and foreign countries	/	The following additional tests are required: Teratogenicity test Chronic toxicity/carcinogenicity combined test Toxicokinetics test (such test is not required for plant ingredient with single component purity < 80%) Long-term human trial safety test (subjects ≥ 100, trial period ≥ 1 year)
High-risk new ingredients: Preservatives, sunscreens, colorants, hair dyes, freckle-removing and whitening ingredients	Registration
Relative high-risk new ingredients: Anti-hair loss, anti-acne, anti-wrinkle (except for physical anti-wrinkle), anti-dandruff, and antiperspirant ingredients	Notification
New ingredients other than preservatives, sunscreens, colorants, hair dyes, freckle-removing and whitening ingredients, anti-hair loss, anti-acne, anti-wrinkle (except for physical anti-wrinkle), anti-dandruff, and antiperspirant ingredients	Notification	The above tests are not required.
New ingredients that do not need to be included in the restricted ingredients list of Safety and Technical Standards for Cosmetics due to safety reasons	/	The above tests are not required.

Compared with high-risk ingredients, the following additional toxicological tests dossiers are required for nanomaterials and high bioactivity ingredients. Nanomaterials should submit a description that toxicological tests are applicable to nanomaterials testing.

New Ingredients		Additional Toxicological Tests	Additional Dossiers Requirements
Nanomaterials	Intended for skin	Skin absorption test/Dermal absorption test Inhalation toxicity test (such test is required when inhalation exposure is possible)	Submit a description that toxicological tests are applicable to nanomaterials testing
Ingredients of oligopeptides, peptides and proteins with high bioactivity that are used in cosmetics for the first time in China and foreign countries	Except for those used in hairs and nails	Skin absorption test/Dermal absorption test Immunogenicity/toxicity test	/

Stability Testing Dossiers Requirements

The stability testing shall be designed according to ingredients’ characteristics, generally including factor influencing tests, accelerated tests, and long-term preservation tests. The requirements for dossiers submission are as follows.

Submit the data, results, conclusions, etc. of the accelerated tests of 3 batches of ingredients produced, or long-term preservation tests of at least 1 year

Submit factor influencing testing documents according to ingredients’ characteristics

For ingredients that are used in cosmetics for the first time both in China and foreign countries, annually supplement long-term preservation testing documents within the 3-year monitoring period

Note: The ingredient storage conditions and shelf life should be determined according to the ingredient’s stability testing.

3) Dossiers Necessary after NCI Registration and Notification

The submission time of safety monitoring and emergency report, and the definition of emergency are clarified.

Safety Monitoring Report

After the NCI are registered or notified with NMPA, the registrant and notifier should collect and sort out information on the NCI usage within the 3-year monitoring period, and submit a report through the registration and notification information system before Mar. 31 each year.

Emergency Report

Emergencies refer to any of the following:

Cosmetics containing NCI caused serious adverse reactions, or the occurrence of adverse reactions or other safety problems may cause a great social impact;
There is evidence that the NCI may have safety problems;
Other countries (regions) discover serious, or group adverse reactions suspected to be caused by that NCI;
Other countries (regions) adjust the regulations and standards of that NCI, strict usage standards, add usage restrictions, or prohibit the use;
Other situations involving the safety of NCI or cosmetics containing NCI.

If any of the above emergencies occur, cosmetic registrant and notifier should collect and sort out the information on the adverse reaction or potential safety hazards, and submit a report through the registration and notification information system within 15 days after the emergency occurs.

2. Requirements for Testing Institutions Qualifications and Testing Methods

Internationally accepted methods and new developed testing methods are newly accepted for NCI physical and chemical test, microbiological test and efficacy evaluation. If a newly developed testing method is used, relevant documents on the applicability and reliability of the method shall be submitted.
If the animal testing alternative methods (not included in the STSC but is validated by an international authoritative alternative method validation agency) are used for toxicological test, the evidence proving the consistency of results obtained from the animal testing alternatives and the traditional toxicological test methods should be submitted.

Please find the detailed requirements in the following table.

Testing Items		Testing Institution Qualification Requirements		Method Requirements
		Qualification	Notes	Method Adoption Basis	Notes
Physical and chemical test, and microbiological test		1. Approved by China Inspection body and Laboratory Mandatory Approval (CMA, in cosmetics field) 2. Approved by China National Accreditation Service for Conformity Assessment (CNAS) 3. Internationally accepted Good Clinical Practice (GCP) or Good Laboratory Practice (GLP)	Should be carried out under the entrustment of a testing institution that meets the qualification requirements	1. Safety and Technical Standards for Cosmetics (STSC) 2. Pharmacopeia of the People’s Republic of China 3. National standards, internationally accepted methods or newly developed testing methods	If a newly developed testing method is used, relevant documents on the applicability and reliability of the method shall be submitted.
Toxicological test				Safety and Technical Standards for Cosmetics (For human trial safety test, may refer to STSC or Pharmacopeia)	1. If the methods not included in the STSC are adopted, it shall follow the national standards or internationally accepted methods, etc. (For human trial safety test, newly developed test methods are also acceptable.); 2. If animal testing alternative methods are used, appropriate Integrated Approaches to Testing and Assessment (IATA) should be selected according to the ingredient's structural characteristics and specific toxicological endpoints to evaluate the ingredient toxicity. If the animal testing alternative methods (not included in the STSC but is validated by an international authoritative alternative method validation agency) are adopted, the evidence proving the consistency of results obtained from the animal testing alternatives and the traditional toxicological test methods should be submitted.
Efficacy evaluation	Preservatives, sunscreens, freckle-removing and whitening, and new efficacy			1. Safety and Technical Standards for Cosmetics (STSC) 2. Pharmacopeia of the People’s Republic of China 3. National standards, internationally accepted methods or newly developed testing methods	If a newly developed testing method is used, relevant documents on the applicability and reliability of the method shall be submitted.
	The new ingredient with other efficacies	/	1. May be carried out by the registrant or notifier on their own or carried out under the entrustment of a testing institution possessed of corresponding capabilities 2. Where the registrant or notifier conducts the test on their own, a self-statement pledging the truthfulness and objectivity of the results shall be provided

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