Stepwise approach of development of dermo‐cosmetic products in healthy and atopic dermatitis paediatric population: safety evaluation, clinical development and postmarket surveillance

Abstract

Background/objectives Paediatric skin, considered sensitive, and infant skin, more susceptible to percutaneous toxicity, require specially formulated cosmetic products. As recently shown, early use of emollients in infants “at risk” of developing atopic dermatitis has shown controversial results in reducing the incidence of atopic dermatitis. Development of dermo‐cosmetic products for this specific population should especially ensure tolerance and safety. In absence of good clinical practice guideline, we propose here a stepwise approach for the development of paediatric cosmetic skincare products. Methods Our stepwise methodology for cosmetics aimed at paediatrics, starts with in vitro assessment of product's ingredients safety, followed by preclinical and clinical evaluations of the final product, including sequentially: (1) Repeated Open Application Test (ROAT), (2) Human Repeated Insult Patch Test (HRIPT), (3) In‐use dermatological and ophthalmological tolerance studies (sequentially in 3a: healthy adults, 3b: healthy paediatric subjects and finally 3c: paediatric patients). We also describe the integrated cosmetovigilance–toxicological surveillance during the clinical development phase and postmarketing. Results As illustrated with one dermo‐cosmetic product intended to be used as a preventative/maintenance treatment for atopic dermatitis in paediatric population, we show that using this stepwise methodology to test a product reduces potential risks of irritation and contact dermatitis in this sensitive population. Conclusion Standardized ethical stepwise development approach is needed to ensure the commercialization of safe and well‐tolerated dermo‐cosmetics for paediatrics. The approach described here could potentially serve as guidance for evaluation of new paediatric cosmetic products.

Nomenclature and clinical phenotypes of atopic dermatitis

“…ACD should also be investigated in paediatric patients; although rates of sensitization are comparable with the general population, ACD is a highly relevant diagnosis in children, and paediatric skin with an immature barrier function is more susceptible to toxicity. 88 In a UK retrospective case study of 114 children aged 3–15 years who were patch-tested over a 3-year period, findings on patch test were positive in 33% of patients with facial dermatitis, 40% with perioral dermatitis, and 86% with eyelid dermatitis. 89 Paediatric patients with moderate-to-severe and early-onset AD have a higher incidence of sensitization to topical products, most commonly to emollients and antiseptics.…”

Potentially harmful substances in moisturizers

“…However, because of the potential side effects of cosmetic products, such as irritant or allergic contact dermatitis, increasing attention has been paid to the necessity of assessment of the safety of such products, especially those intended to be used in the pediatric population, in which skin barrier function is immature. 4 Thus, it is possible that chronic use of moisturizers containing haptens may lead to a vicious cycle of inflammation and skin barrier disruption that requires repeated applications of products. This in turn may play a role in increasing skin permeability and, subsequently, FA.…”

Surveillance of dermo-cosmetic products: a global cosmetovigilance system to optimise product development and consumer safety

“…The adverse reactions are analysed by the internal safety committee, including toxicologists, pharmacists, and dermatologists, and all cases of intolerance are further discussed during the consolidated analyses of safety. If the adverse reactions observed during the clinical studies are considered non-compatible with the nature of the product and the targeted population, the clinical development of the product can be terminated and formulation changes implemented [14].…”

“…As an illustration, we describe the development of a keratolytic dermo-cosmetic product indicated for the management of cradle caps and seborrhoeic dermatitis [17] on face and scalp. According to our internal guidelines dedicated for the development of this type of dermo-cosmetic product [14], the formula was evaluated through several clinical studies. The different studies, along with the key safety results, are presented in table 1.…”

“…A robust and global cosmetovigilance system is expected to identify any potential change in a product's safety profile, take preventive or corrective measures if necessary, and disseminate the information for continuous product improvement. We recently proposed a stepwise, standardised approach for the development of safe and well-tolerated dermo-cosmetic products for a paediatric population [14]. The present paper focuses on the key features of a structured, reactive, and rigorous cosmetovigilance system through practical examples of the surveillance of dermo-cosmetic products throughout their lifecycle.…”