Sunscreen products as medical devices – what does this mean for the consumer? Critically examine the relevance of IR radiation and the role of photolyases.
Our seasonal outdoor recreational activities make sun protection a perennial topic every year. Primary prevention is widely discussed in the press from April to August and is accompanied by a wide range of recommendations.
Guiding questions for this article
So what are the trends this year? This article is dedicated to three topics that are examined in more detail and critically scrutinized – because not everything that passes for a trend is based on solid consumer information.
The vast majority of sunscreen products in Europe and Switzerland are classified as cosmetics or cosmetic products . For a few years now, sunscreen products have also been advertised as products from the medical devices category. What is behind this new category and what benefits do such products offer?
The first sunscreen products that came on the market were intended to enable tanning without sunburn (erythema) (primarily protection against UV-B radiation). The importance of UV-A radiation has also been recognized. Since the mid-1980s, products have been offered that also protect in the UV-A range. After the turn of the millennium, the importance of infrared (IR) radiation for the skin was intensively discussed. The potential damage to deeper skin structures from IR radiation led to the development of sunscreen products that also offer IR protection. What is it exactly?
Conventional sunscreen products are used to prevent skin damage and work by reducing UV radiation. Changes in skin cell DNA that have already occurred can no longer influence them. Recent data indicate that topical application of DNA regeneration enzymes selectively reverses UVB-induced changes that have already occurred. Against this background, products containing DNA regeneration enzymes such as photolyases are now available. How do such preparations work?
Sunscreen products in the medical devices category
Unlike in the USA or Australia, where sunscreen products are classified as medicinal products, in Europe and Switzerland these products are declared as cosmetics or cosmetic products. For the first time in Switzerland (2007) and later throughout Europe, certain sunscreen products were also advertised as medical devices. When it comes to the question of what lies behind this category of medical devices and what benefits such products offer, a look at the current legal situation will help.
In Switzerland, medical devices are regulated by the Federal Law on Medicinal Products and Medical Devices (812.21, Heilmttelgesetz, HMG). They are defined as products intended for medical use and […]whose main effect is NOT achieved by a medicinal product. The Swiss and the European law regulate here a tremendously large product class. Accordingly, the set of rules is also very extensive. The definition defines medical devices […]as any instrument, apparatus, device, software, substance or other article, whether used alone or in combination, including software specifically intended by the manufacturer to be used for diagnostic and/or therapeutic purposes and used for the proper functioning of the medical device, intended by the manufacturer to be used for human beings for the following purposes: Detection, prevention, monitoring, treatment or alleviation of disease; […]and whose principal intended action in or on the human body is not achieved by pharmacological or immunological means or metabolically, but whose mode of action may be assisted by such means.
Cosmetic products can be distinguished from this group. Cosmetic products are defined in the Ordinance on Foodstuffs and Utility Articles (LGV; SR 817.02) as substances or preparations intended to come into external contact with the various parts of the human body (skin, hair system, nails, lips and intimate regions) or with the teeth and mucous membranes of the oral cavity, […]for the sole or predominant purpose of cleaning them, perfuming them, changing their appearance or affecting body odor, or to protect them or keep them in good condition. References of any kind to a disease-curing, disease-soothing or disease-preventing effect of articles in use (e.g. medicinal or therapeutic properties, disinfecting or anti-inflammatory effects, medical recommendations) are prohibited (Art. 31 para. 3 LGV). There are exceptions! In the case of dental and oral care products, references to caries-preventing and other preventive dental properties are permitted if they can be scientifically proven (Art. 31 para. 4 LGV). For cosmetic products, the Food Act currently does not provide for general protection against deception. Deception is only inadmissible if it may result in damage to health. A typical example would be the sun cream that does not have the specified protection factor.
The legal texts quickly make it clear that, in contrast to cosmetic products, a so-called healing promise may be made in the advertising of medical products. Actinca® lotion from Spirig Pharma AG (now Galderma S.A.) was the first sunscreen product in the world to be notified and marketed as a medical device in Switzerland and Europe. In clinical studies A) effective protection against various types of light skin cancer has been demonstrated, such as a 53% decrease in actinic keratoses and no new invasive squamous cell carcinomas within 2 years after regular use of the product, as well as B) prevention of cutaneous lupus erythematosus symptoms [1,2] substantiated.
Meanwhile, in Switzerland, another cosmetically very appealing product – SunsiMed by Pierre Fabre – has been launched, which promotes the prevention of actinic keratoses, skin cancer (except melanoma) and photoaging. Numerous other similar medical products have appeared on the market throughout Europe. According to Swiss and European legislation, a clinical evaluation must be available for each product. This is based (A) based on a critical evaluation of the results of all clinical trials conducted; or B) on a critical evaluation of the relevant currently available scientific literature on the safety, performance, design characteristics, and intended use of the product. The purpose is to demonstrate the similarity of the product to the product to which the data refers. It can be guessed that there is a large scope here to include many scientific studies in an evaluation. To identify and evaluate the added benefit of such products, it is recommended to obtain a complete collection of published clinical data WITH the advertised medical device.
IR protection
In recent years, IR protection has been widely reported [3] and some sunscreen suppliers advertise IR protection concepts. IR radiation is lower in energy than ultraviolet light, but penetrates deeper into the skin compared to UV light – regardless of skin type. There it damages the collagen structure and thus accelerates skin aging. Mitochondria play a special role in IR-induced skin damage. IR radiation causes the formation of reactive oxygen radicals in the mitochondria, which in turn trigger “retrograde signal transduction”. Signal transduction ultimately leads to an increase in the expression of the enzyme matrix metalloproteinase-1 (MMP-1, collagenase-1), which results in the breakdown of collagen in the skin and thus accelerated skin aging. Whether IR-induced increased oxidative stress is also associated with increased carcinogenicity is currently unclear. Various groups have created special mixtures of different antioxidants designed to neutralize the reactive oxygen radicals in skin cells and their components created by short-wave infrared light. These effects are well documented in numerous in vitro systemsper se. However, in the only clinical trial to date, this effect is modest [4]. The previous data are also questioned because the amount of IR radiation used experimentally, far exceeds the amount of IR radiation that a sun-hungry vacationer on the beach or workers in certain occupations (glass blowers, iron workers) get [5]. This calls into question the usefulness of topical IR protection.
IR protection involves neutralization of an endogenous damaging agent (reactive oxygen radicals) newly created by IR radiation, while UV protection involves absorption of a damaging exogenous agent (photons). There are also no IR filter substances that can be incorporated into sunscreen products! In short, this means that IR protection is damage limitation and UV protection is damage prevention. Based on the data available to date, the importance and benefits of topical IR protection are still unclear.
Photolyases
Conventional sunscreen products work by reducing UV radiation. Protection is never complete and is sometimes referred to as passive sun protection. Today, products containing DNA regeneration enzymes such as photolyases are marketed under the term active photoprotection. The active sunscreen is designed to specifically correct radiation-induced changes that have already occurred. The neutralization of reactive oxygen radicals in skin cells and their components by antioxidants can also be understood as active sun protection (see also IR protection).
Photolyases are enzymes involved in the repair of DNA. They accomplish, among other things, the resolution of cyclobutane-pyrimidine dimers (CPD), which are formed when DNA is exposed to ultraviolet radiation. Photolyases were discovered by Claud S. Rupert in 1958. The discovery marked the beginning of the field of DNA repair as a scientific discipline. He demonstrated that bacterial DNA damaged by UV light was repaired by an enzyme that uses blue light as an energy source. The reaction mechanism was described as follows: UV light converts two adjacent pyrimidines, including thymines, into a cyclobutane-pyrimindine dimer. The enzyme, known as photolyase, uses the energy of blue light to cleave the two “abnormal” bonds between the thymins, converting the tymindimer back into two “normal” thymins. Photolyases thus repair DNA and eliminate the undesirable effects of UV radiation. A student of Claud Rupert – Aziz Sancar – along with two other scientists received the Nobel Prize in Chemistry in 2015 for elucidating DNA repair mechanisms [6]. Photolyases represents a very large group of proteins with similar structures but very divergent functions [7,8]. A precise designation of the photolyase used is therefore always required for any publication in which photolyases are used.
A number of small studies have shown that topical application of photolyase in products with and without sunscreen (filters) resulted in a reduction of UVB-induced cyclobutane-pyrimidine dimers and apoptotic cell death. Also in xeroderma pigmentosum patients, the use of a sunscreen containing photolyase resulted in a significant reduction of neoplasms such as actinic keratoses, basal and squamous cell carcinomas [9,10,11]. These results are also consistently appreciated in various reviews [12,13]. Often, the scientific papers support the special effect of sunscreen products with photolyases and are at the same time part of the notification of sunscreen products with photolyases as medical devices (see above).
In addition to the small number of cases, it is noticeable in the scientific papers that the active principle of action (photolyase) and the active substance carrier are hardly described in sufficient detail. Exactly which photolyase is involved and from where the active ingredient comes in which form can rarely be determined. Photolyase, produced from photosynthetic plankton Anacystis nidulans, is commercially available, for example, from raw material distributor ProTec Ingredia Ltd. UK as Photosomes V in multilamellar liposomes (pH 7-8). The content or activity of photolyase in the liposomes is determined by the manufacturer using in vitro testsand published in a technical bulletin. This distributor recommends incorporating the liposome suspension as a 1% additive into a suitable topical vehicle. Whether the liposomes are actually stable in the chosen topical form and photolyase activity is maintained (even during storage) remains unknown. However, photolyases are not only found in active sunscreens, but also in a number of cosmetic products (e.g. FILORGA SKIN-ABSOLUTE DAY® or cellcosmet CellLift Serum). The fact that no further information is presented with these products is not expected by anyone due to the legislation, as they are cosmetic products. It is also not explicitly required for a medical device, but one may expect a lot more from a product used in a clinical trial for the treatment and prevention of potentially malignant skin lesions.
Photolyase are proteins with a molecular mass of more than 100,000 daltons. For molecules with a molecular mass of more than 500 Daltons it is already difficult or impossible to overcome the stratum corneum [14]. Against this background, it is difficult to imagine the mode of action and the effect of photolyase after topical application.
Despite many positive clinical reports (studies mostly refer to the product Eryfotona AK-NMSC®, ISDIN SA, Barcelona, Spain) on the effect of photolyase in sunscreens with very high sun protection to reduce A) UVB-induced cyclobutane-pyrimidine dimers and of B) neoplasms such as actinic keratoses, basal and squamous cell carcinomas lack a convincing explanation for the results of the clinical reports. Furthermore, in most cases a lege artis description of the products used in the clinical trials is missing.
Based on current data, there is no reason to use these products preferentially or exclusively.
Conclusion
For sunscreens notified as medical devices, claims such as “prevention of actinic keratoses, skin cancer (except melanoma) and photoaging” or “effective protection against various types of light skin cancer” are permitted. This allows a clear differentiation to be made from conventional sunscreens, which are assigned to the category of cosmetic products. In order to clearly identify and evaluate the additional benefits of such products, it is recommended to obtain a complete collection of published clinical data WITH the advertised medical device.
IR protection involves neutralization of an endogenous damaging agent (reactive oxygen radicals) newly created by IR radiation, while UV protection involves absorption of a damaging exogenous agent (photons). Since the amounts of IR radiation used experimentally to date far exceed the amounts of IR radiation that a sun-hungry vacationer on the beach or workers in certain professions (glassblowers, ironworkers) get, today’s reports are also questioned. Based on the data available to date, the importance and benefits of topical IR protection are still unclear.
Despite many positive clinical reports on the effect of photolyase in sunscreens with very high sun protection to reduce UVB-induced cyclobutane-pyrimidine dimers or neoplasms such as actinic keratoses, basal and squamous cell carcinomas, a convincing explanation for the results of the clinical reports is missing. Based on this data, there is no reason to use these products preferentially or exclusively.
Take-home-messages
- In the case of sunscreen products that are notified as medical devices, healing promises are permitted – in contrast to products that are listed as cosmetics.
- The added benefit of such medical devices can only be determined after reviewing all published clinical data on the advertised product.
- IR protection is the neutralization of an endogenous damaging agent newly created by IR radiation (reactive oxygen radicals), while UV protection is the absorption of a damaging exogenous agent (photons).
- Based on the data available to date, the importance and benefits of topical IR protection are still unclear.
- Despite many positive reports on the effects of photolyase in sunscreens, a convincing explanation for the results of the clinical reports is lacking.
Conflict of interest: Prof. Christian Surber is an employee of the Dermatological University Hospital Basel and Zurich. In the past, he has been associated in various capacities with the following companies: Actelion Pharmaceuticals, Allschwil; BASF Personal Care and Nutrition GmbH, Ludwigshafen; Galderma SA, Lausanne; CureVac GmbH, Tübingen;Janssen Research & Development, Beerse; LEO Pharma GmbH, Neu-Isenburg; Novartis Consumer Health SA, Nyon; Novartis AG, Basel; Roivant Sciences, Inc, Durham; Spirig Pharma AG, Egerkingen.
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