Regulatory Updates of Animal Testing in China and Other Countries

ChenYe,Wang Chris

ChemLinked,China

Animal testing for the sake of cosmetic safety has always been a very controversial topic since it’s often viewed as cruel due to its harm,or outright death,of the animals subjected to them.In the early years,animal testing was adopted to assess product safety and allergenicity during the R＆D of cosmetics and daily chemical products.Since then,we have seen significant technological advancements to the extent that people argue that animal tests have become largely redundant.As a response,crueltyfree advocates have made huge headway in lobbying governments to ban animal testing.In this report,I will look at those major advancements in the global push towards a global ban on animal testing.

1 China

1.1 Background of animal testing

China’s mandatory animal testing requirements have been a major stumbling block stymying the entry of many overseas cruelty-free cosmetics brands.For a long time,cosmetic companies were obliged to utilize NMPA-approved (National Medical Products Administration) labs to perform animal tests on their cosmetic finished products or ingredients even if they have been assessed as "safe" and have already been marketed in other countries.In other words,NMPA technical review experts did not accept testing results drawn from non-animal testing methods.

As an increasing number of China’s trading partners introduced national bans on animal testing due to the growing demand by the public for crueltyfree testing methods,it led to the result that the Chinese cosmetics market has some divergences in standards and regulations compared to wider international market.As a response to that China,in order to re-align its cosmetics regulations and industry capacities with global practices and trends,has gone to great lengths to phase out animal testing of cosmetics over the past few years.The significant ones are:removal of mandatory animal testing for domestic non-special use cosmetics filing.

In 2013,the previous competent authority-CFDA (now NMPA) issued Requirements for Filing of Domestic Non-Special Use Cosmetics stipulating that mandatory animal testing could be avoided for domestic non-special use cosmetics if reliable safety assessment reports were provided.The announcement came into force on June 30,2014.

It is the first time for Chinese authorities to put forward specific measures to reduce animal testing and was a significant milestone for China on its way to modernize its animal testing policy and re-align its regulatory framework with global cruelty-free trends.

1.1.1 Animal testing exemption for CBEC imports

In 2016 China initiated a regulatory reform on its cross-border e-commerce policies,under which the CBEC-traded commodities were subject to mandatory pre-market registration or filing.However,as the reform sparked considerable controversy among the public,a transitional policy that “temporarily” exempted the pre-market approval for first imported cosmetics,infant formula,etc.via CBEC channel was launched in 15 CBEC pilot cities such as Shanghai and Hangzhou.

On November 21,2018,the CBEC transitional policy was officially extended.As per the new rules,cosmetics imported in this mode shall be supervised as personal articles,exempt from customs import license,and not subject to cosmetic regulations.Hence the significant time and financial investment needed to comply with Chinese labeling requirements and mandatory toxicology testing requirements could be avoided.Therefore it offers an excellent market access route for international cosmetic stakeholders to circumvent animal testing.

1.1.2 Landmark guidance for cosmetic safety risk assessment

Safety risk assessment is regarded as an effective means to evaluate cosmetic safety.On November 10,2015,the previous CFDA released aGuidance for Cosmetic Safety Risk Assessmentfor public consultation,which provides for the first time a complete technical standard on risk assessment of cosmetics in China.The draft version contains nine sections offering clarification on a number of issues revolving around cosmetic risk assessment,such as risk assessment procedures,toxicological research,ingredient risk assessment,cosmetic product safety evaluation,and risk assessment report compilation.

The guidance arrives at a time when China is in desperate need of such an inclusive technical reference to aid authorities in counteracting growing cosmetic safety issues and enhance the efficiency of market inspection.There have been sporadic initiatives made in previous years by CFDA to bolster the risk assessment of cosmetics.“Risk Assessment Guidance for Potential Safety Risk Substance in Cosmetics” released in August 2010 and the “Notice regarding Relevant Affairs of Adjusting Cosmetic Application and Record-keeping Management”released in November 2013 were both steps forward in addressing risk assessment requirements but fell sorely short of offering systemic and comprehensive guidance for practical implementation.

However,this guidance has been pending and in process for nearly five years.On July 29,2020,a brand new draft Technical Guidelines for Cosmetic Safety Assessment was worked out by the NMPA to supersede the 2015 guidance.The new draft further refines the requirements for safety assessment and will hopefully be the last version before promulgation.

1.1.3 Development progress of alternative testing methods

Alternative testing methods serve as viable surrogate markers in the assessment of potential toxicities,adverse effects,and hazards/risks associated with the use of cosmetics and can reduce reliance on the use of animal testing.

On November 11,2016,China included the 3T3 NRU Phototoxicity Test as a toxicology test method into Cosmetic Safety and Technical Standards for Cosmetics.Then on August 15,2017,the Skin Corrosion:Transcutaneous Electrical Resistance Test was accepted as an in vitro test method for skin corrosion.

On March 22,2019,NMPA approved and included nine testing methods in the Cosmetic Safety and Technical Standards 2015,of which four standards are newly approved alternatives to animal testing.These standards areShort Time Exposure In Vitro Test Method (STE),Skin Sensitization:Local Lymph Node Assay:DA (LLNA:DA),In Chemico Skin Sensitization:Direct Peptide Reactivity Assay (DPRA) and Skin Sensitization:Local Lymph Node Assay:BrdU-ELISA (LLNA:BrdU-ELISA).They came into effect for the relevant cosmetic registration/filing and post-market surveillance testing on January 1,2020.

Furthermore,in recent years,a larger number of domestic organizations such as the National Institutes for Food and Drug Control and Zhejiang Institute for Food and Drug Control have developed a partnership with the international nonprofit organization Institute for In Vitro Sciences.The goal of these collaborations is to open more in vitro toxicity testing laboratories and to establish more alternatives to animal testing methods.

1.2 Regulation and supervision updates in 2020

2020 is crucial year in China's cosmetic sector,which witnessed a historical transition in the overarching regulatory framework from the outdated Cosmetics Hygiene Supervision Regulations (CHSR) to the modern Cosmetic Supervision and Administration Regulation (CSAR).In regard to animal testing management,one of the most concerned issues of the industry,China has encouragingly introduced some policy shifts under the new regulatory regime.

1.2.1 Animal testing exemption

On November 5,2020,NMPA released the second draft of Instructions for Cosmetic Registration and Notification Dossiers for public comments.One of the most high-profile updates in the draft is a de facto end to animal testing for general cosmetics.General cosmetics here refer to all the products complying with the definition of cosmetics within the CSAR,except for the special cosmetics,namely hair dyes,hair perming products,freckle-removing,and whitening products,sunscreens,anti-hair loss products,and cosmetics claiming new efficacy.

Specifically,relevant toxicological tests of general products can be exempted provided that the manufacturer has obtained relevant GMP certification from the cosmetic regulatory authority of the local government,and the product safety risk assessment results can fully verify the product's safety.

However,there are still three circumstances where animal testing will be required:The product is for specific use by children or infants; The product uses new cosmetic ingredients that are in the safety monitoring period;The notifier,domestic responsible person,and actual manufacturing enterprise are listed as the key supervision targets according to the quantitative grading results.

Notably,the exemption is still subject to certain limitations as currently there are very few overseas government agencies that can issue an official GMP or ISO certification.Instead,cosmetic associations or international standardization organizations generally issue the GMP certificates for overseas companies.

1.2.2 Safety assessment

Regarding safety assessment documents,the Instructions for Cosmetic Registration and Notification Dossiers indicate that general cosmetics eligible for animal testing exemption can submit safety assessment reports rather than toxicological test reports when applying for notification.In the case of products claimed to be used by infants and children,both the toxicological test reports and product safety assessment reports should be submitted when applying for registration/notification.Highlighted in red are the safety assessment requirements for animal testing exemptions.

Special cosmetics:toxicological test report +abstract of the safety assessment

General cosmetics:approach 1:toxicological test report + abstract of the safety assessment.Approach 2:application for toxicological test exemption + safety assessment report

Cosmetics claimed to be used by infants and children:safety assessment report + toxicological test report (necessary Safety Assessment Documents for Cosmetic Registration and Notification)

Moreover,a separate safety assessmentrelated regulation,the draft Technical Guidelines for Cosmetic Safety Assessment,was opened for public consultation on July 29,2020.The Guidelines clarify the basic requirements of safety assessors,the requirements and operating guidelines for safety assessment reports,attach corresponding samples,and set transitional measures to ensure a smooth transition to the new regulations.

1.2.3 Alternative methods

Regarding alternative methods,China has approved the addition of 4 new alternatives to the animal testing methods in theCosmetic Safety and Technical Standards2015 on March 22,2019.As of January 1,2020,these four new methods officially came into effect(Table 1.),bringing the total of alternative methods to seven.Significantly,the majority of the 7 methods are designed for cosmetic ingredients,and there is only one alternative method to determine photoallergenicity for finished products.

Table 1.Testing method in China

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Additionally,the Instructions for New Cosmetic Ingredient Registration and Notification Dossiers released on November 5 regulates that international alternatives recognized by an international authoritative alternative validation agency such as OECD,ICCR,ICCVAM,EURL-ECVAM,JaCVAM,etc.can be accepted for the notification or registration of new cosmetic ingredients.

To use the data derived from international alternatives,companies shall comply with 2 requirements:The appropriate Integrated Approaches to Testing and Assessment(IATA) shall be selected to evaluate the toxicity based on the characteristics of the new ingredient and the specific toxicological endpoint.Supporting documents proving the consistency of results obtained from the alternatives and the existing toxicological testing methods in China shall be submitted.

For the supporting documents,they can be related research papers and scientific works that have been openly published and include detailed analysis or testing reports issued by internationally accepted Good Laboratory Practice (GLP) compliant labs.They shall include a brief description of the testing method research process,comparative research data of not less than 10 test substances,result analysis,conclusions,original texts,etc.

Similar to the animal testing exemption for general cosmetics,the conditions for the acceptance of international alternatives are also stringent.It is quite difficult for companies to provide such supporting documents as the existing qualified research papers and scientific works are rare,and the fees for conducting the required testing and obtaining the testing reports are costly.

2 South Korea

2.1 Animal testing ban

South Korea banned mandatory animal testing on cosmetics starting from February 3,2017.No responsible cosmetic distributor shall distribute or sell any cosmetics for which animal testing was conducted,or cosmetics manufactured (including manufacturing by consignment) or imported using ingredients for which animal testing was conducted.There are several exceptions to this rule,which are as follows:where animal testing is needed to determine the standards for using ingredients requiring a specific restriction on usage,such as preservatives,coloring or sunscreens or to assess hazards of cosmetics ingredients,etc.posing risks to public health; Where animal testing is needed because no alternative to animal testing (referring to non-animal testing or testing on a limited number of animals or reducing animal pains,and recognized as such by the MFDS) exists; Where animal testing is needed to export cosmetics in accordance with the statutes and regulations of the export partner country; Where animal testing is needed for product development in accordance with the statutes and regulations of the importing country; Where ingredients developed through animal testing conducted under other statutes and regulations are used for the manufacture,etc.of cosmetics; Other cases prescribed by the MFDS,where it is otherwise impractical to conduct alternatives to animal testing.

2.2 Guidelines for animal testing alternatives released in 2020

South Korea released 3 Guidelines for the animal testing alternative methods in 2020,which are:In chemico skin sensitization:amino acid derivative reactivity assay (ADRA); Vitrigel-eye irritancy test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage; Reactive oxygen species (ros)assay for photoreactivity.

These guidelines include principles of the test,considerations and limitations,method of the test,approval requirements,results,and report of the test.

2.3 All the 24 guidelines for animal testing alternative methods

Until now,South Korea has released 24 guidelines for alternative methods.The following table includes these details(Table 2).

Table 2.24 guidelines for alternative methods in South Korea

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3 Australia

In February 2019,Australia passed the amendments to the Industrial Chemicals Bill 2017,which mainly aims to establish a new regulatory scheme—Australian Industrial Chemicals Introduction Scheme (AICIS) to replace the existing National Industrial Chemicals Notification and Assessment Scheme (NICNAS) for the management on the introduction of industrial chemicals.The bill also encompasses provisions to prohibit reliance on new animal testing data for supporting the introduction of chemicals solely used as cosmetic ingredients.

On July 1,2020,the new scheme and the animal testing ban officially took effect.Notably,the prohibition only affects new ingredients used exclusively in cosmetics,whether produced domestically or imported.It does not impact cosmetic products already on the market,and new ingredients that have multi-functions across different product categories are exempt.

Besides,the reform allows for the use of internationally recognized alternatives to animal testing,such as in-vitro testing methods validated by the Organization for Economic Co-operation and Development (OECD),in silico (computer-based)methods,and read-across methods (information from existing animal test data of a similar chemical).

4 Global country ban on animal testing

Global ban country list and in the process of banning in Table 3 and 4.

Table 3.Animal testing ban in global ban country list

Table 4.Animal testing ban in the process of banning

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