China Specifies Practices of Cosmetic Adverse Reaction Monitoring and Reporting

Background

On October 1, 2022, with the implementation of Measures for the Management of Cosmetic Adverse Reaction Monitoring, China NMPA launched the upgraded new version of the National Cosmetic Adverse Reaction Monitoring System to facilitate stakeholders to submit reports. Where cosmetic registrants, notifiers, entrusted production enterprises, operators, and/or medical institutions discover or become aware of any cosmetic adverse reaction, they shall submit a report through the adverse reaction monitoring system.

On November 25, 2022, the Center for Drug Reevaluation and the National Center for Adverse Drug Reaction (ADR) Monitoring of China published the draft of Cosmetic Adverse Reaction Collection and Reporting Guidelines for Cosmetic Registrants and Notifiers (Trial) for public feedback. ¹ On April 19, 2024, the finalized version of the Guidelines was released. ²

The Guidelines provides instructions for registrants and notifiers on the collection and reporting of cosmetic adverse reactions, including stages from collection, recording, transmission, to report confirmation, analysis and evaluation, submission, quality control, and record management. The key contents of the Guidelines are as follows:

1. Adverse reaction collection

Regarding adverse reaction collection, the Guidelines clarifies that registrants and notifiers shall establish effective information collection channels with consumers, entrusted production enterprises, cosmetic operators, and medical institutions, and actively collect adverse reactions of their cosmetics sold on the market.

For instance:

Collecting Adverse Reaction from Consumer: Registrants and notifiers are required to make their contact information, including telephone numbers and email addresses, readily available to consumers through product labels, official websites, and/or other accessible platforms. This facilitates the easy reporting of cosmetic adverse reactions by consumers;
Collecting Adverse Reactions from Entrusted Production Enterprises: Registrants, notifiers, and entrusted production enterprises are encouraged to include provisions in written agreements to ensure that the entrusted production enterprises promptly notify the registrants and notifiers of any adverse reactions. The agreements should also clearly outline the specific requirements for collecting and transmitting information related to adverse reactions.

2. Adverse reaction recording and transmission

As per the Guidelines, registrants and notifiers are responsible for maintaining the authenticity, completeness, and accuracy of adverse reaction information. To achieve this, registrants and notifiers should meet the following requirements when recording and transmitting adverse reactions:

Preserve the original records of adverse reaction-related information, such as phone call records, emails, and screenshots. Additionally, they should establish monitoring records based on these original records;
During the transmission process, any deletions or omissions are prohibited. If any information is not collected or if any change is made to the original records, such modifications should be duly noted. Registrants and notifiers are encouraged to specify a time limit for transmitting adverse reaction information, thereby ensuring compliance with the required reporting timeframe.

3. Adverse reaction report confirmation

In terms of report submission, the Guidelines emphasizes the importance of confirming the compliance with reporting principles and the validity of adverse reaction reports collected through different channels. Specifically:

Reporting Principle: Adverse reactions related to cosmetics should be reported immediately once suspicion arises. That is, if the possibility of human damage related to the use of cosmetics cannot be ruled out, the situation shall be reported;
Valid Report: A valid report should include four essential elements: the identification of the reporter, the identification of the person experiencing adverse reactions, information about the adverse reactions, and details of the cosmetics used.

For cosmetic adverse reactions that are determined not to be submitted to monitoring institutions, the reasons for non-submission must be documented, and monitoring records should be maintained.

4. Adverse reaction analysis and evaluation

Upon confirming adverse reactions, registrants and notifiers are required to conduct a thorough analysis and evaluation of the severity of the reactions as well as the relationship between the adverse reactions and the respective products. If necessary, they should perform a comprehensive self-inspection of the product’s ingredients, formulation, production processes, production quality management, as well as storage and transportation practices, among other factors that may contribute to adverse reactions.

Severity of the Reactions

The severity of adverse reactions is categorized into three levels: general adverse reactions, serious adverse reactions, and adverse reactions that may have a significant social impact. In the case of serious adverse reactions and those that may have a significant social impact, in addition to conducting a thorough analysis and evaluation, registrants and notifiers are required to compile a self-inspection report and submit it to the provincial-level monitoring institutions and provincial-level medical products administration departments within 20 days and 10 days respectively after being informed.

The Guidelines provides the following explanations for determining serious adverse reactions and adverse reactions that may cause significant social impact:

Serious Adverse Reactions

Adverse Reactions that May Have a Significant Social Impact

1) Causing temporary or permanent loss of functions, and affecting normal function of human body and social ability, such as permanently unhealable skin lesions, scar formation, permanent hair loss, and obvious appearance damage, etc.;

2) Causing systemic damages to the human body, such as abnormal liver and kidney functions, anaphylactic shock, etc.;

3) Causing hospitalization or circumstances deemed necessary for hospitalization by medical institutions;

4) Causing other severe damages to the human body, endangering life, or causing death.

May cause a large social impact or cause serious damage to multiple people in a certain area due to the normal use of the same cosmetic product.

Relationship Between the Adverse Reactions and the Respective Products

When conducting relevance evaluation, registrants and notifiers should perform a comprehensive relevance analysis based on available information, relevant knowledge, and experience. In China, the relevance evaluation process is primarily guided by five principles:

Time Relationship: Is there a reasonable temporal association between the use of a cosmetic and the occurrence of an adverse reaction?
Discontinuation Consistency: Does the discontinuation of adverse reaction align with the discontinuation of the suspected cosmetic?
Repetition: Does the same reaction recur upon reusing the suspected cosmetic?
Exclusion of Other Factors: Have other factors such as other diseases and other contacts been adequately considered and excluded as potential causes?
Laboratory Examination: Do the results of laboratory examinations indicate a correlation between the adverse reaction and the use of the cosmetic?

5. Adverse reaction report submission

Registrants and notifiers are required to timely submit reports of adverse reactions within the specified timeframe through the National Cosmetic Adverse Reaction Monitoring System. They should also ensure the maintenance, including timely update of the information. The reporting time limit begins from the day when the registrants and notifiers first discover or become aware of the adverse reaction, which is recorded as day 0. The date of day 0 shall be accurately recorded for proper documentation.

Report Items	Time Limit
General cosmetic adverse reactions	To be reported within 30 days from the date of discovery
Serious cosmetic adverse reactions	To be reported within 15 days from the date of discovery
Cosmetic adverse reactions that may have a significant social impact	To be reported within 3 days from the date of discovery

6. Adverse reaction monitoring records management

The Guidelines strictly regulates the management of adverse reaction records, which include monitoring records and original records.

Monitoring records must be objective, authentic, and accurate. They should contain, at a minimum, the reporter's information, details of the person experiencing adverse reactions, symptoms or signs, severity of the adverse reactions, occurrence date, discovery or learning date, reporting date, and the name of the cosmetics used. For serious adverse reactions and those may have a significant social impact, registrants and notifiers should also record possible causes, analysis and evaluation, follow-up risk control measures, and other relevant information;
Registrants and notifiers are required to assign a unique, consecutive, and traceable number to each collected cosmetic adverse reaction. This number should enable easy referencing of the adverse reaction reports submitted to the national monitoring system;
Both physical records and electronic documents are acceptable. Records should be properly stored to prevent accidental loss and damage. They should be clear, readable, easy to understand, and appropriately classified and cataloged. Records must be retained for a minimum of 3 years from the date of reporting.