EUROPEAN COMMISSION Brussels, 15.10.2019 COM(2019) 479 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 (2018)





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 (2018)

1.Introduction This is the thirteenth 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. The animal testing of finished cosmetic products has been prohibited in the EU since 11 September 2004, and the testing of cosmetic ingredients since 11 March 2009 (testing ban). Since 11 March 2009, the marketing in the EU of cosmetic products and their ingredients which have been tested on animals in order to meet the requirements of Directive 76/768/EEC has also been prohibited (2009 marketing ban). This marketing ban applied to all but the most complex human health effects (endpoints) that needed to be tested to demonstrate the safety of cosmetic products in the absence of alternative non-animal tests (repeated-dose toxicity, reproductive toxicity and toxicokinetics); the European Parliament and the Council decided that the ban would take effect on 11 March 2013 (2013 marketing ban). On 11 March 2013, the Commission adopted a Communication on the animal testing and marketing ban and on the state of play in relation to alternative methods in the field of cosmetics. This Communication confirmed the Commission’s commitment to maintaining the 2013 deadline. Therefore, the marketing ban became fully applicable as of 11 March 2013, irrespective of the availability of alternative non-animal tests. 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) of the Cosmetics Regulation. However, to date there have been no derogations granted under this provision. The information on compliance with the testing and marketing bans and the impact of the bans in Section 2 is based on contributions from Member States, mainly covering the years 2017-2018. The information on the progress made in the development, validation and legal acceptance of alternative methods in Section 3 is largely based on the 2018 status report from the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) of the Commission’s Joint Research Centre (JRC). 2.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. 2.1.Inspections and compliance National market surveillance activities and controls monitoring compliance with the testing and marketing bans were mostly carried out in the course of regular inspections on cosmetic products, or of regular inspections on cosmetic products as part of general control activities. No inspection programmes were specifically carried out to monitor compliance with the testing and marketing bans. Compliance was usually verified through checks of PIFs conducted by competent national authorities. Based on inspections carried out by market surveillance authorities, one Member State reported amongst the hundreds cases of control three cases of non-compliance with the marketing ban, following which the companies were asked to remedy the infringement. Some other Member States reported very few cases where the infringement was actually a lack of complete documentation to prove compliance with the bans, rather than non-compliance with the ban itself (see Section 2.2.). 2.2.Difficulties encountered with monitoring the ban and suggestions for improvement

The very large majority of the Member States who monitored compliance with the testing and marketing bans did not report any difficulties in carrying out compliance checks. As in the previous reporting periods, the main issue raised by a few Member States was the fact that the checked PIFs were incomplete with regard to data on animal testing. This information is necessary to verify compliance with the bans. The issue of a very limited number of incomplete PIFs regarding data on animal testing was confirmed by six Member States. The checked PIFs often contained limited toxicological data of ingredients used in the finished product. This is because suppliers of ingredients do not provide cosmetic product manufacturers with adequate toxicological information, or they only attach a declaration stating that an ingredient has not been tested on animals for the purposes of the Cosmetics Regulation. It sometimes happens that manufacturers cannot gain access even to that information since their ingredient suppliers refuse to provide them with it. When cosmetic products are imported from non-EU countries, manufacturers issue a declaration to the responsible person stating that neither the cosmetic products being imported nor their ingredients have been tested on animals in view of assessing their safety pursuant to the Cosmetics Regulation. However, they do not provide them with any information on tests carried out in accordance with other legislation. One Member State argued that checking the PIF at the premises of a responsible person is very difficult and time consuming given the required scope, the specific training for inspectors and the need for appropriate technical equipment in place (implying increased financial costs). It is also quite challenging to ensure suitable training for responsible persons and safety assessors. The competent authorities properly addressed all the few above-mentioned shortcomings. Manufacturers and responsible persons 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 alternative methods. If the information was not provided, the consequence was the withdrawal of the product(s) from the market. 2.3.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. However, two Member States reported that SMEs do not have sufficient knowledge about the testing and marketing bans and sufficient financial resources needed for cost-intensive toxicological tests on new ingredients. Furthermore, the cosmetic ingredients suppliers do not provide them with the required safety data voluntarily. Another problem concerns safety assessors, who are insufficient in number. At the European level there are no available lists from which responsible persons could select safety assessors to commission them to draw up a safety report. In particular SMEs therefore have problems finding a suitable safety assessor. Since they do not very often understand the specific requirements of Article 18 or of Article 11 of the Cosmetics Regulation, they assume that the safety report drawn up for them by a safety assessor is in accordance with the requirements of Annex I to the Cosmetics Regulation and do not have any doubts about its correctness. On the question of how the testing and marketing bans have affected the innovativeness of the cosmetics sector, most Member States did not provide any information. Two Member States reported that some SMEs face difficulties, due to the absence of alternative methods, to fully replace animal testing, and thus to compose a comprehensive safety file for a cosmetic product containing a new cosmetic ingredient, particularly with regard to skin sensitisation, repeated-dose toxicity and reproductive toxicity. 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 used exclusively in cosmetic products e.g. new UV filters or preservatives. One Member State emphasized the need for developing alternatives to animal testing, in particular for repeated-dose toxicity, reproductive toxicity and toxicokinetics. These are areas where complete replacement of animal testing with alternative methods is not yet possible. These shortcomings can potentially make it difficult to assess fully the safety of new cosmetic ingredients. The absence of full replacement alternative methods for the most complex toxicological areas is indeed 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. 3.Progress made in the development, validation and legal acceptance of alternative methods Considerable progress was made on several fronts in the development, validation and regulatory acceptance of alternative approaches to animal testing in 2018. Research and development activities continued in areas for which replacement, reduction and refinement (3Rs) solutions are more difficult to find. For regulatory toxicity testing, research projects focused on repeated dose and reproductive toxicity testing, on chemical mixtures and endocrine disruptors. These projects are either based on read-across case studies or aim at developing new in vitro methods and integrating in vitro methods and in silico computational technologies in integrated assessment and testing strategies to translate mechanistic understanding of toxicity into risk assessment methodology. In the area of carcinogenicity, EURL ECVAM is currently exploring how mechanistic data across toxicity endpoints (based primarily on existing in vivo and in vitro OECD test guidelines) could be best combined, instead of taking them in isolation, to waive redundant testing and, ultimately, improve carcinogenicity testing. The well-advanced areas of topical toxicity, skin sensitisation and genotoxicity were complemented with additional in vitro methods or combined (in silico and in vitro) approaches which have either already been adopted or are currently being reviewed and discussed in international fora. 3.1.Progress in the EU 3.1.1. Research and development activities Major research and development activities on methods alternative to animal testing are ongoing in the EU. EU-ToxRisk is a European collaborative project funded by the EU Framework Programme for Research and Innovation, Horizon 2020 (H2020), to advance mechanism-based toxicity testing and risk assessment. With a budget of over EUR 30 million, it was launched in January 2016 and will last for 6 years. The project, which builds on the results of SEURAT-1, has developed several case studies in the complex fields of repeated dose and developmental/reproductive toxicity testing, including for endocrine disrupters. Several industries, including some cosmetics companies, are currently establishing collaborations with the project, which also closely interacts with regulatory agencies and EURL ECVAM.

The Innovative Medicine Initiative (IMI), as part of H2020, also supports various projects aiming at developing safety testing procedures without animal, namely for quality control of vaccines and safety assessment of drugs. These projects receive €35M from the European Commission plus an equal in-kind contribution from the pharmaceutical sector. Other H2020 programmes support relevant research activities, such as the Euromix project aimed to develop an animal-free strategy for the risk assessment of mixtures of multiple chemicals, several projects related to the safety of nanomaterials, and finally numerous projects from the European Research Council (ERC) and Marie Sklodowska Curie that develop new in vitro and in silico tools that could be integrated into animal-free safety testing. 3.1.2.Validation and legal acceptance of alternative methods EURL ECVAM is mandated under Article 48 and Annex VII of Directive 2010/63/EU to validate alternative test methods at EU level and promote regulatory acceptance of these. The European Union Network of Laboratories for the Validation of Alternative Methods (EU-NETVAL) has continued to support the EURL ECVAM validation studies. The network has also helped develop guidance documents and training materials for good in vitro method practices. The validation of alternative methods intended for regulatory use has progressed on a number of fronts including novel methods for predicting the skin sensitisation potential of chemicals, assessing the leaching (bioelution) of chemicals from metal alloys, and for determining acute toxicity in fish. Two EURL ECVAM validation studies deal with methods for the identification of endocrine disruptors and involve the EU-NETVAL. Several multi-stakeholder discussions on validation took place in various fora which indicate that although well-established validation principles are still relevant today, the process of validation needs to be continually adapted to keep pace with scientific and technological progress. More details on these activities can be found in the 2018 EURL ECVAM status reports. 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 the Tracking System for Alternative methods towards Regulatory acceptance (TSAR). 3.1.3.The European Partnership for Alternative Approaches to Animal Testing The European Partnership for Alternative Approaches to Animal Testing (EPAA) is a public-private partnership between the European Commission, eight European trade associations and 36 individual companies from the relevant business sectors. The partners are committed to pooling knowledge and resources to accelerate the development, validation and acceptance of alternative approaches to animal use in regulatory testing. The overall aim is the replacement, reduction and refinement (3Rs) of animal use in regulatory testing. In 2018, the work of EPAA included seven projects to facilitate the promotion, validation, acceptance and implementation of 3R alternatives in European regulatory testing and decision-making, and to promote international harmonisation of regulatory testing. In each of the projects the over-arching objective is to apply the 3Rs without compromising safety; indeed, several of these projects examine how human (or veterinary) safety and product quality can be assured and sometimes even improved by the use of new integrated approaches based primarily on in vitro methods. In 2018, one new project started and six ongoing projects progressed well. A new project on ‘Applying non-animal strategies for assessing skin sensitisation’ was launched, with the main objective to organise and run a knowledge-sharing workshop. This new project builds on the continuing successful progression of the project on optimised strategies for assessing skin sensitisation. EPAA projects are good examples of the unique synergies that EPAA and its partners achieve to advance alternative methods, by bringing together the relevant industry sectors, regulators, academia and public interest, and to promote the 3Rs principle in the regulatory environment in Europe. EPAA continues to seek new opportunities for 3Rs alternatives and, following the highly successful first Partners’ Forum held in 2017 on the subject of toxicokinetics and read-across, a second Forum was held in November 2018 on repeated-dose toxicity. The output of these fora, as well as information on the projects and EPAA's other activities are published on the EPAA website. These activities build on existing research initiatives, identify synergies amongst sectors and seek to bridge the gap between science, innovation and regulation. 3.1.4.Dissemination of information on alternatives The dissemination of information about alternative approaches (e.g., in vitro techniques and in silico models) and of chemical datasets contributes to the advancement and strengthening of the 3Rs knowledge. In this context, publicly accessible information systems not only can facilitate the engagement of the scientific community through the sharing and exploitation of existing data and information, but they can also inform regulators and assist educational and training activities. The information systems and services provided and coordinated by EURL ECVAM serve this purpose, including the above-mentioned Tracking System for Alternative methods towards Regulatory acceptance (TSAR), the DB-ALM collection of in vitro methods, and the QSAR Model Database on in silico methods. In addition, EURL ECVAM has published, following the Commission Decision on the reuse of Commission documents (2011/833/EU), the results of the assessments it conducted on available 3Rs knowledge sources and related education and training activities. EURL ECVAM has also carried out a number of awareness-raising activities regarding alternatives to animal testing, such as knowledge sharing and training.