EUROPEAN COMMISSION Brussels, 10.7.2018 COM(2018) 531 final REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT AND THE COUNCIL on the development, validation and legal acceptance of methods alternative to animal testing in the field of cosmetics (2015-2017)



REPORT FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT AND THE COUNCIL on the development, validation and legal acceptance of methods alternative to animal testing in the field of cosmetics (2015-2017) 1.Introduction This is the 12th Commission report on the development, validation and legal acceptance of methods alternative to animal testing in the field of cosmetics. Under Article 35 of Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products (the Cosmetics Regulation), each report must include information on: -progress made in the development, validation and acceptance of methods alternative to animal testing; -the Commission’s progress on obtaining the OECD’s acceptance of the alternative methods validated at EU level; -progress on third-country recognition of the results of safety tests carried out in the EU using alternative methods; -the specific needs of small and medium-sized enterprises (SMEs). This report also informs the European Parliament and the Council of compliance with the deadlines for the animal testing bans set out in Article 18(1) and of related technical difficulties, pursuant to Article 18(2) of the Cosmetics Regulation. Article 18(1) prohibits the testing on animals of finished cosmetic products and of cosmetic ingredients (testing ban), as well as the marketing of finished cosmetic products and of cosmetic products containing ingredients tested on animals (marketing ban), to meet the requirements of the Cosmetics Regulation. Under Article 18(2) of the Cosmetics Regulation, the report should also cover any derogation from Article 18(1) granted in accordance with Article 18(2). However, to date there have been no derogations granted under this provision. The information in Section 3 on compliance with the testing and marketing bans and the impact of the bans is based on contributions from Member States, mainly covering the years 2015-2016. The information in Section 4 on the progress made in the development, validation and legal acceptance of alternative methods is largely based on the 2016 and 2017 status reports from the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) of the Commission’s Joint Research Centre. Together, they cover the period from October 2015 to September 2017. 2.Clarification of the scope of the marketing ban by the Court of Justice In the European Federation for Cosmetic Ingredients case, the Court of Justice made an important clarification on the interpretation of the marketing ban as regards animal testing carried out in non-EU countries to comply with the cosmetics legislation of a third country. The main question examined by the Court was whether Article 18(1)(b) may be interpreted as prohibiting the placing on the EU market of cosmetic products containing ingredients that have been tested on animals outside the EU to comply with the cosmetics legislation of a third country. The Court concluded that: ‘Article 18(1)(b) of Regulation (EC) No 1223/2009[…] must be interpreted as meaning that it may prohibit the placing on the European Union market of cosmetic products containing some ingredients that have been tested on animals outside the European Union, in order to market cosmetic products in third countries, if the resulting data is used to prove the safety of those products for the purposes of placing them on the EU market’. 3.Compliance with the testing and marketing bans and their impact In practice, the main way of verifying compliance with the testing and marketing bans is the cosmetic product information file (PIF). The ‘responsible person’, who has to ensure compliance with the relevant obligations of the Cosmetics Regulation (usually the manufacturer or the importer), must keep a PIF for every cosmetic placed on the EU market. The PIF must include the cosmetic product safety report and data on any animal testing performed relating to the development or safety assessment of the cosmetic product or its ingredients. The Commission Communication of 11 March 2013 provides further guidance as to what information should be included in the PIF. 3.1.Inspections and compliance As in the previous reporting period, monitoring activities and checks related to compliance with the testing and marketing bans were mostly carried out in the course of regular inspections on cosmetic products as part of general control activities. There were no inspection programmes specifically dedicated to monitoring compliance with the testing and marketing bans. Compliance was mainly verified through checks by the competent national authorities on cosmetic products’ PIFs.

Only three Member States reported not monitoring compliance with the bans as part of these inspections. One of these Member States argued that it was not possible to verify the absence of animal tests in the context of general market surveillance, as it is a complex process. Based on inspections carried out by market surveillance authorities, a Member State reported two cases of infringement of the testing and marketing bans, following which the companies were asked to remedy the breach. Some other Member States reported cases where the breach was actually a lack of (complete) documentation proving compliance with the bans, rather than non-compliance with the ban itself (see Section 3.2.). 3.2.Difficulties encountered with monitoring the ban and suggestions for improvement Of the Member States who monitored compliance with the testing and marketing bans, the very large majority did not report any difficulties in carrying out compliance checks. In the previous reporting period, the main issue raised by several Member States was the fact that PIFs were incomplete with regard to data on animal testing – this information is necessary to verify compliance with the bans. The Commission therefore asked the Member States specific questions on this aspect, in particular regarding what type of data was missing and what measures had been taken. The issue of PIFs being incomplete as regards data on animal testing was confirmed by seven Member States. Most of these Member States did not mention or note any changes to the situation compared to the previous period. They did not specifically monitor the issue of incomplete PIFs or monitored it through continued reviews of PIFs as part of market surveillance activities. The issues with PIFs were the following: the information on animal testing or alternatives in the PIF (or declaration thereof) was absent or insufficiently detailed (e.g. it did not reference the ingredients and the finished product, or it did not mention testing under other regulatory frameworks and a justification of the need for this); the toxicological data was insufficient for some cosmetic ingredients (for instance the ingredients’ suppliers did not provide toxicological data on the ingredients but only a declaration). Three Member States noted a correlation between the size of the operator (SMEs) and the issue of incomplete information on animal testing in the PIF. Four Member States raised the issue with respect to cosmetics imported into the EU, where information from the non-EU suppliers was missing. Two Member States noted that importers and/or SMEs lack knowledge regarding the application of the animal testing ban requirements. One of those Member States highlighted the difficulty for SMEs of finding an appropriate safety assessor for their product and noted that the safety assessment was sometimes incomplete. (However, this point is not specifically linked to the animal testing ban.) Nevertheless, the competent authorities appear to be properly addressing the few above-mentioned shortcomings. Operators with PIFs that did not provide complete animal testing information were required to take corrective action. They had to provide the missing information, for instance by asking their suppliers for that information or by producing toxicological data based on alternatives. If the information was not provided, the ultimate consequence was the withdrawal of the product(s) from the market. However, one Member State stressed the limits of this approach with regard to missing toxicological data: for new ingredients, alternative methods would not always be available or affordable for SMEs. Four Member States suggested that guidelines/ information should be developed on the PIF and on the application of the animal testing ban. One of these Member States also reported that their authorities engage with operators, in particular SMEs, through for instance information events to explain the regulatory requirements. Other types of difficulty were reported in a few instances. One Member State mentioned the difficulty of verifying the accuracy of an operator’s declaration that no animal testing had been performed. This is due to the fact that supply chains for cosmetic ingredients are very long. Another Member State reported the issue of the reliability of information provided with respect to cosmetics imported from non-EU countries. Two Member States argued that checking compliance with the bans is a lengthy and complex process, as it requires in-depth verification of documents, specific training for inspectors and appropriate technical equipment (implying increased financial costs). In particular, according to one of these Member States, the PIF checks are hampered by the fact that the PIF is only accessible onsite, with no possibility of making copies and carrying out checks at the competent authority’s offices. One Member State raised the issue of market surveillance of cosmetic products for which the ‘responsible person’ is based in another Member State, in which case the authority has no direct access to the PIF, or where the Member State in which the ‘responsible person’ is based takes time to reply to an information request. This difficulty is not specific to the animal testing ban, but is linked to PIF checks in general. 3.3.Ban-related issues encountered by manufacturers, in particular SMEs, and the bans’ impact on the innovativeness of the cosmetics sector Most Member States did not report any cases where a manufacturer, in particular an SME, was not able to place a cosmetic product on the market due to an inconclusive safety assessment of the product or ingredient caused by a lack of alternatives to animal testing. On the question of how the testing and marketing bans have affected the innovativeness of the cosmetics sector, most Member States either did not provide any information or reported that this information was not available to them or had not been received from the industry. However, five Member States reported the issues below. One Member State mentioned feedback received from some operators regarding difficulties in placing cosmetic products on the market due to insufficient data to prove product safety without animal testing. Another Member State reported the concern raised by its cosmetics industry that it was not possible to perform a full safety assessment of a cosmetic ingredient in the absence of animal testing and that it was not possible to develop new ingredients for cosmetic applications. Another Member State mentioned feedback from an operator, which stated that, although it is not impossible to develop innovative products, it takes more time and involves more costs, as alternative (in vitro and in silico) methods require new knowledge and more time to be analysed. Three Member States mentioned the need for alternatives to animal testing to be developed, in particular for repeated-dose toxicity, reproductive toxicity and toxicokinetics. These are areas in which it is not yet possible to completely replace animal testing with alternative methods. These shortcomings can potentially make it difficult to fully assess the safety of new cosmetic ingredients. The absence of full replacement alternative methods for the most complex toxicological areas is widely recognised. Therefore, research is ongoing to develop these methods. For the other toxicological areas, progress has been made towards the validation and regulatory acceptance of alternative methods. In particular, work is being done to develop ‘integrated approaches to testing and assessment’ (IATAs). This is explained further in Section 4 below.

4.Progress made in the development, validation and legal acceptance of alternative methods As mentioned in the last Commission report, significant progress has been made in the development, validation and regulatory acceptance of alternative methods, for skin irritation/corrosion, serious eye damage/eye irritation and skin sensitisation. Current research into and development of methods alternative to animal testing mainly focus on integrating a variety of testing and non-testing methods. These include in vitro technologies, bioinformatics and computational toxicology, and they are grouped into the IATAs mentioned above. IATAs have been developed and internationally harmonised in the areas of skin irritation/corrosion and serious eye damage/eye irritation, and are in the process of being approved for skin sensitisation. The more complex human health effects (endpoints) still present challenges and require more research. This is the case, for example, for acute and chronic systemic toxicity, areas in which significant knowledge gaps currently limit the development of IATAs. 4.1.Progress in the EU 4.1.1.Research and development activities Major research and development activities on methods alternative to animal testing are ongoing in the EU. The EUR 50 million SEURAT-1 research initiative, co-funded by the Commission and Cosmetics Europe (the European personal care association) and completed in 2015, developed a workflow to assess safety without relying on animal testing, designed for cosmetic ingredients but also applicable to other types of chemicals. The outcome was published in 2017 and is freely accessible online. EU-ToxRisk, the integrated European ‘flagship’ programme driving mechanism-based toxicity testing and risk assessment for the 21st century, is a major collaborative project funded by the EU framework programme for research and innovation, Horizon 2020. With a budget of over EUR 30 million, it was launched in January 2016 and will last for six years. The project, which builds on the results of SEURAT-1, aims to make progress towards animal-free safety assessments and tackles complex areas of toxicology, such as repeated-dose and reproductive toxicity. The first eight case studies have progressed considerably, establishing collaborations with the US Tox21 and the Commission, through EURL ECVAM. Several other large Horizon 2020 research projects to assess chemical mixtures have begun in recent years, including EuroMix and EDC-MixRisk. EuroMix aims to develop a strategy for the risk assessment of mixtures of chemicals from multiple sources, while EDC-MixRisk focuses on improving the risk assessment of exposure to mixtures of endocrine-disrupting compounds. Both explore mixture assessments including in vitro and in silico methods. The Commission collaborates on these projects through EURL ECVAM. The human biomonitoring project HBM4EU, in which the Commission and several EU agencies are involved, includes one work package dedicated to mixtures. 4.1.2.Validation and regulatory acceptance of alternative methods EURL ECVAM is mandated under Article 48 of and Annex VII to Directive 2010/63/EU to validate alternative test methods at EU level and promote their regulatory acceptance. The progress of a test method from submission towards acceptance as a recognised test method for use in various sectors and its final adoption into a regulatory framework can be followed through a new version of the tracking system for alternative test methods towards regulatory acceptance (TSAR). 4.1.2.1.Evaluation and validation of test methods In the period covered by its 2016 and 2017 status reports, EURL ECVAM evaluated 11 test submissions. It carried out or assessed (in the context of submissions) several validation studies in the areas of endocrine disruption, developmental neurotoxicity, skin sensitisation and genotoxicity. In addition, the EURL ECVAM Scientific Advisory Committee peer-reviewed validation studies carried out by the industry in the areas of (serious) eye damage / eye irritation, skin sensitisation and skin irritation. In 2017, EURL ECVAM published a recommendation on the use of non-animal approaches for skin sensitisation (allergy) testing. The performance of a number of ‘defined approaches’ based on different types of non-animal data is considered to be comparable with that of the standard animal test for identifying potential skin allergens. that these approaches be used where applicable and appropriate, instead of the standard animal test. As a consequence, a project is currently running within the OECD test guidelines programme, under the leadership of EURL ECVAM, the US Environmental Protection Agency and Health Canada, to develop a guideline based on defined approaches for skin sensitisation testing. The European Union Network of Laboratories for the Validation of Alternative Methods (EU-NETVAL) has supported the EURL ECVAM validation studies. It has also helped develop guidance documents and training materials for good in vitro method development and provided input into drafting OECD technical guidance on that topic. It is worth noting that, in future, validation work may have to focus on standards for classes of methods rather than on validating individual methods. More details on these activities can be found in the 2016 and 2017 EURL ECVAM status reports. 4.1.2.2.Regulatory uptake

Since the last Commission report, Commission Regulation (EC) No 440/2008, which brings together all regulatory accepted testing methods at EU level, has been updated once. Under the REACH Regulation, the in vivo tests previously required for skin irritation/corrosion, serious eye damage / eye irritation and skin sensitisation have been fully replaced by in vitro testing. The last amendment to the annex on skin sensitisation was adopted in April 2017. 4.1.2.3.European Partnership for Alternative Approaches to Animal Testing The Commission and industry representatives continue to facilitate the regulatory acceptance of alternative methods and approaches under the European Partnership for Alternative Approaches to Animal Testing (EPAA). According to its updated action programme for 2016-2020, the EPAA plans to: ·address science and technology gaps and optimise translation from research to regulatory practice; ·improve intra- and inter-sectoral collaboration and coordination; ·facilitate regulatory acceptance of additional sources of evidence in the current regulatory framework; ·communicate scientific reality; and ·‘educate the educated’ (improve access to information, training opportunities and tools). In 2017 the EPAA launched the Partners Forum, which provides an opportunity for all EPAA members to share information about their existing research initiatives, learn from each other’s experience and build synergies across business sectors to potentially speed up the development and acceptance of alternative methods for regulatory purposes. The 2017 forum was dedicated to toxicokinetics and ‘read-across’, and similar events will be organised annually focusing on an area that is of current common interest to several sectors. EPAA has been very active, for example in the area of skin sensitisation in recent years, in making progress on and facilitating the uptake of alternatives. The project on optimised strategies for assessing skin sensitisation evaluated the reliability and predicting capacity of the three most advanced skin models. Other recent or ongoing EPAA projects have focused on alternative approaches for toxicokinetics (exposure), acute toxicity and genotoxicity testing, and for vaccine potency and safety assessment. 4.1.2.4.Dissemination of information on alternatives The availability of information on alternatives is crucial. Therefore, information has been compiled in several databases at EURL ECVAM, including TSAR, the DB-ALM database on in vitro methods and the QSAR model database on in silico methods. EURL ECVAM has also carried out a number of awareness-raising activities regarding alternatives to animal testing, such as knowledge-sharing and training. In December 2016, the Commission held a scientific conference in Brussels to engage the scientific community and relevant stakeholders in a debate on how to exploit cutting-edge advances in biomedical and other research in the development of scientifically valid alternatives to animal testing. The event was one of the four actions announced in the Commission Communication responding to the European citizens’ initiative ‘Stop vivisection’. 4.2.Progress at international level 4.2.1.Activities at OECD level The Commission, through EURL ECVAM, plays an active role at OECD level in the regulatory acceptance of alternative methods and their international adoption. The OECD test guideline programme is the main instrument for promoting a globally harmonised safety assessment of chemicals. From 2016 to 2017, a total of 24 new and updated test guidelines were approved, of which four were based on in vitro methods (on skin sensitisation, skin corrosion and endocrine disruption). A summary of the adoption status of test guidelines in the OECD from 2011 to 2017 based on alternative methods can be found in Annex 1 to the 2017 EURL ECVAM status report. In addition, 16 guidance documents or supporting documents were approved during that period, in particular the guidance document on the IATA to testing and assessment for serious eye damage / eye irritation, which is a basic requirement for the safety assessment of chemicals in many regulations. Activities within the OECD working party on hazard assessment also play an important role in improving technical convergence on alternative methods at international level. OECD member countries work together to improve and harmonise assessment methodologies for chemicals and collectively gain experience in the development of IATAs which has become a priority over recent years as an alternative solution to animal testing.