68 REGULATION HPC Today vol. 15(4) 2020 systemic absorption of its ingredients must be demonstrated to exceed 100 (1, 17). Other challenges in the evaluation of new substances are the animal testing ban (17). To be listed as a new preservative, UV filter, or colouring agent, the European Scientific Committee of Consumer Safety only accepts toxicity data from scientifically acceptable alternative methods (17). The EU Cosmetics Regulations have also inspired the new Biocidal Products Regulations (6). For example, hand disinfectants and mosquito repellent products for humans must be free of non-active ingredients that do not comply with the annexes in the Cosmetics Regulations. APPROVAL AND BANNING The competent authority requires evidence of the quality, safety and usefulness of medicinal products, while class II and III medical devices are granted conformity approval through a notified body before being placed on the market (18). Their safe maintenance should also be demonstrated. Class III devices with drug substances also require consultations with a competent authority on the medicinal aspects of the device. Cosmetics and class I medical devices do not require any pre-market authorization or any external pre-market review before being launched. However, the regulatory compliance of these products is continuously monitored by the authorities in the member states. Examples of sales bans issued in one EU Member state (Sweden) on cosmetics due to non-conformance of the products with the Cosmetics Regulations are given in Table 2. The European Commission is alerted daily by the national authorities to dangerous products due to e.g. the presence of illegally used ingredients, microbial contamination and other impurities. These alerts are sent through the rapid alert system (RAPEX) for dangerous non-food products and include information about the risks posed and the measures taken at the national level to prevent or restrict their marketing (19). (class I and II) if they are free from ingredients with significant pharmacological, immunological or metabolic action. Such substance-based medical devices are found on the European market for treatment of e.g. head lice with suffocating oils, warts with pH-lowering acids, acne with pore-opening acids and dermatitis with physical protecting/occlusive fats. To ensure conformity of class II-III devices with the legislation, a Notified Body must be consulted. These bodies are commercial organisations charging fees to the manufacturers for their work, and their identity is shown by a 4-digit number close to the CE mark on the product. Biocidal products are “any substance or mixture... intention of destroying, deterring, rendering harmless, preventing the action of, or otherwise exerting a controlling effect on, any harmful organism” (6). For example, hand sanitizers destroying microorganisms on the skin surface belong to the biocidal category, whereas deodorants and antiperspirants are generally classified as cosmetics due to their main intended use to correct body odour via perfuming and action on the skin microflora (2). Cosmetic products are defined on the target of the application and the intended function: ‘Any substance or mixture intended to be placed in contact with the various external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance and or/correcting body odours and/or protecting them or keeping them in good condition’ (3). The recently implemented regulation on cosmetics claims also emphasises the need to protect consumers from misleading claims (15). Six common criteria are established: legal compliance, truthfulness, evidential support, honesty, fairness and informed decision making (15). SAFETY RULES Cosmetics are used daily on healthy as well as on diseased skin. The European Union’s (EU) Cosmetics Regulation lays down all rules for products’ and ingredients’ safety, where substances under consideration are taken up in its annexes (1). Currently, 1638 substances are prohibited (e.g. retinoic acid, corticosteroids, oestrogens, nicotine, minoxidil) and 316 are restricted, whereas 154 colorants, 56 preservatives and 31 UV filters are approved. The hazards and the risks of using any of the other approx. 25 000 listed substances are evaluated in the mandatory Cosmetic Product Safety Report (CPSR) (8), compiled by the Responsible Person (1). Cosmetics should be demonstrated to be safe under normal and reasonably foreseeable use, where, for example, the margin of safety after Figure 1. A schematic view on the classification of a topically applied product as a cosmetic product, medical device, medicinal product or a biocidal product.