Pharma & Cosmetics in the GCC Region Latest cosmetics and cosmeceutical trends and regulatory aspects. Medical claims Prof. Heyam Saad Ali, Ph.D. Pharmaceutics Department Dubai Pharmacy College Thursday, February 11, 2016

Outline Definitions Regulatory authority- cosmetics/ Cosmeceuticals Borderline classification- medical, biocide –cosmetics. Case-by-case decision on individual borderline products-medical claims Safety/tests assessment. Conclusion Pharma & Cosmetics in the GCC Region

Section I Definitions Pharma & Cosmetics in the GCC Region

Poll Question What do Cosmetics mean? A) Articles intended to promote attractiveness. B) Products intended to kill bacteria. C) Substances intended to be placed into cavities of the body D) Answer is A Pharma & Cosmetics in the GCC Region

Definition – Cosmetics Articles intended to be placed in contact with various external parts of the body, for: Cleansing Beautifying Promoting attractiveness Altering appearance Excludes soaps Pharma & Cosmetics in the GCC Region

Definition – soaps How FDA defines "soap“ Not every product marketed as soap meets FDA's definition of the term. FDA interprets the term "soap" to apply only when the bulk of the nonvolatile matter in the product consists of an alkali salt of fatty acids and the product's detergent properties are due to the alkali-fatty acid compounds, The product is labeled, sold, and represented solely as soap [21 CFR 701.20]. Products that meet this definition of soap are regulated by the Consumer Product Safety Commission   (CPSC), not by FDA. Pharma & Cosmetics in the GCC Region

Definition – Drugs How does the law define a drug? The FD&C Act defines drugs, in part, by their intended use, as "articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease" and "articles (other than food) intended to affect the structure or any function of the body of man or other animals" [FD&C Act, sec. 201(g)(1)]. Pharma & Cosmetics in the GCC Region

Definition: A medicinal product A medicinal product is: any substance or combination of substances that may be used by or administered to human beings to: Restoring, Correcting or Modifying a physiological function by exerting a pharmacological, immunological or metabolic action. They are subject to medicine safety ,labelling legislation and medicines control. Pharma & Cosmetics in the GCC Region

Definition – Food & Food supplement products: Food (“or foodstuff”) means any substance or product, whether processed, partially processed or unprocessed, intended to be, ingested by humans. Food supplement the purpose of which is to: Supplement the normal diet. Providing nutritional & physiological benefits. They are concentrated sources of nutrients, amino acids & vitamins, in marketed in dose form” Pharma & Cosmetics in the GCC Region

Definitions – Medical device They are means to assist in functioning on the human body, have no pharmacological, immunological or metabolic effects. They include : Any instrument, apparatus, appliance, material or other article, whether used alone or in combination. They are necessary for its proper application intended to be used for human beings for the diagnosis & prevention purposes. control of conception. Pharma & Cosmetics in the GCC Region

Definition-Cosmeceuticals It is a term that has found application and recognition to designate the products at the borderline between cosmetics and pharmaceuticals. A cosmeceutical is an ingredient with medicinal properties, which manifests beneficial topical actions: Impart desirable aesthetic effects. provide protection against degenerative skin conditions e.g UV exposure damage. Pharma & Cosmetics in the GCC Region

Pharma & Cosmetics in the GCC Region

Examples of botanical Cosmeceuticals: photo-protective effect-antioxidants-in vivo Pharma & Cosmetics in the GCC Region

Section II Regulatory Authority Pharma & Cosmetics in the GCC Region

Regulates the following classes Pharma & Cosmetics in the GCC Region

Poll Question Do you think cosmetics are regulated by FDA? Yes No Limited: Only through two Federal laws. Pharma & Cosmetics in the GCC Region

FDA authority- laws for marketed cosmetics regulation The two most important laws pertaining to cosmetics marketed in the United States are: The Federal Food, Drug, and Cosmetic Act(FD&C Act) The Fair Packaging and Labeling Act (FPLA). FDA regulates cosmetics under the authority of these laws. Congress authorizes federal laws including FDA, to create regulations. A change in FDA's legal authority over cosmetics would require Congress to change the law. Pharma & Cosmetics in the GCC Region

Poll Question Do you think cosmetics are subject to approval by FDA?  Yes  No Cosmetics are not subject to mandatory FDA review or pre-marketing approval. But the claims made about drugs are subject to high scrutiny by the (FDA) review and approval process Pharma & Cosmetics in the GCC Region

Requirements for marketed cosmetics The FD&C Act prohibits the marketing of adulterated or misbranded cosmetics “Adulteration” refers to violations involving product composition--they contain restricted or prohibited ingredients, contaminants, processing, packaging, or shipping and handling. “Misbranding” refers to violations involving improperly labeled or deceptively packaged products. Enforcement law & actions against : Firms or individuals undergo violation, Adulterated & misbranded marketed cosmetic products Pharma & Cosmetics in the GCC Region

Requirements of Appropriate labelling Who regulates advertising claims? While FDA regulates labeling for cosmetics and drugs, advertising claims are regulated by the Federal Trade Commission.

Regulatory Aspects: Cosmeceuticals The FD&C Act does not recognize any such category as "cosmeceuticals."  there is no legal definition called Cosmeceuticals, the term has no meaning under the law. Cosmeceuticals are not subject to FDA review because Pharma & Cosmetics in the GCC Region

Regulatory Aspects: Cosmeceuticals current status Some countries have called the classes of products that fall between the two categories of cosmetics and drugs as follows: For example, Japan has ‘Quasi-drugs’; Thailand has ‘controlled cosmetics’ Hong Kong has ‘cosmetic-type drugs’. The regulations of Cosmeceuticals have not been harmonized between the USA,European, Asian and other countries. Pharma & Cosmetics in the GCC Region

Regulatory Aspects: Cosmeceuticals status Impact: Consumers: It is difficult for consumers to determine whether ‘claims’ marketed about these products unless there is a valid approval by the FDA or an equivalent agency about their actions, efficacies & safety. Experts Experts are calling for increased regulation of Cosmeceuticals to insure mandatory proof of their safety. Pharma & Cosmetics in the GCC Region

Section III Borderline Products- situations, medical claims Case-by-case decision on individual borderline products Pharma & Cosmetics in the GCC Region

Definitions – Borderline Products Overview Some products are hard to distinguish from cosmetics, food or medicines because they claimed to have attributes of cosmetics and therapeutics. These products are called borderline products until their status has been decided. Then, regulated accordingly. Definition: They are products having attributes of cosmetics and therapeutics. They have been claimed by using words or phrases which present a medicinal intent. Examples of words: cures; prevents, treats, heals & restores Some product claim that it kills germs and microbes, as it would fall under the biocide regulation Pharma & Cosmetics in the GCC Region

-Types of borderline products The types of products which may fall in to the borderline category include: Cosmetics ( the following table ) Food products, in particular, food supplements Herbal products (aromatherapy) Medical devices Biocides Machinery/Laboratory equipment (used in cosmetic techniques) Pharma & Cosmetics in the GCC Region

Major Cosmetic Product Categories, that fall within these borderline Face and nail- Tinted bases/foundation with SPF - Lip products with SPF 2. Skin Care- Moisturising products with SPF for dermal application - Sunbathing products with sun protection for a secondary purpose SPF ≥4 and ≤15 3. Skin care  - Anti-bacterial skin products 4. Skin care- Anti-acne skin products  5.Oral hygiene- Products for the care of teeth and mouth   6. Hair care- Anti-dandruff products Pharma & Cosmetics in the GCC Region

Borderline Products- Situations-determination the type of the product, for regulation To determine whether a product is a cosmetic, medicinal, borderline or medical device experts in (MHRA) regulatory authority have to: I. Examine the product on case-by-case decision on individual borderline and II. Determine whether a product is a cosmetic, medicinal, borderline, or medical device based on the following four criteria: 1. Function or intended use: implicitly &explicitly ) 2. Presentation: (Type of product e.g shampoo, chewing gum,); 3. Mode of application: (e.g externally or on the Mucous membranes of the oral cavity); 4. Composition: (e.g prohibited & restricted, color, aromatherapy, (NE FDA conc., etc). Pharma & Cosmetics in the GCC Region

Borderline Products- What's the importance of "intended use"?- Under the law, how “a cosmetic ”: cosmetic products regulation depends mainly on how they are intended to be used. FDA determines a product’s intended use based on the following factors : 1-claims made in the labeling, 2-claims made in the on websites, and 3-claims made in the in advertising, 4-claims made in the depends on consumers expectation. 5- words or phrases showing a product is marketed. Finally, we make decisions on a case-by-case basis. Pharma & Cosmetics in the GCC Region

It is not regulated as a cosmetic product Not altering structure or function in human or animal. NO It is a cosmetic product must meet its requirements. Pharma & Cosmetics in the GCC Region

Medical Claims-borderline Products- Examples Decisions on A Case-by- case Basis IV Section

Borderline Products- Examples decisions on a case-by-case basis. Type of product: shower gel. Question: is this product is a cosmetic or a drug? Answer: The product is intended only to cleanse the body or to make a person more attractive, it’s a cosmetic. So, if a product such as a shower gel contains perfume or cologne, then it is intended only to make a person smell good, it’s a cosmetic. Pharma & Cosmetics in the GCC Region

Type of products: soaps, lotions, and massage oils containing “essential oils” , is it a drug? Claims: ease pain, relax muscles, or help you sleep are drug claims aromatherapy. Interpretation: this product is intended for affecting the structure or function of the body, by easing pain & relaxing muscle, therefore, it’s a drug & marketed as “aromatherapy.” 2-The fact that a fragrance material or other ingredient comes from a plant doesn’t keep it from being regulated as a drug. Drug requirements: Under the law, drugs must meet requirements such as FDA approval for safety, physical & chemical stability during shelf and effectiveness before they go on the market. . Pharma & Cosmetics in the GCC Region

– Borderline cosmetics- antidandruff shampoo Question: Is this product is a cosmetic or a drug? Answer: This product has two intended uses. its intended use is to cleanse the hair. Also, the intended use is to treat dandruff This product meets the definitions of both cosmetics and drugs. Therefore the required regulation of both a cosmetic and a drug, must be met. Pharma & Cosmetics in the GCC Region

Biocide product- toothpastes that contain fluoride Question: Is this product is a cosmetic or a drug? Answer: This product has two intended uses. its intended use is to cleanse the teeth. Also, the intended use is to kill the microbe. This product meets the definitions of both cosmetics and drugs . Therefore the required regulation of both a cosmetic and a drug, must be met. Conclusion: Therefore, this product falls under the remit of Directive on Biocidal Products

TYPE OF PRODUCT – Tongue brushes releasing a preparation Question: Is a tongue brush which releases anti-microbial substance a cosmetic product? Answer & interpretation: This product meets the definitions of both cosmetics & drugs, because The intended use for cleaning, perfuming, changing appearance of the teeth. Also, this product meet the definition of a drug product because The intended use for activation of an anti-microbial process by releasing an anti-microbial substance, such as silver. Conclusion: Therefore, this product falls under the remit of Directive on Biocidal Products.

TYPE OF PRODUCT – Washable, temporary “tattoos” Question: Is a washable, temporary “tattoo” (i.e. a little picture which is moistened and subsequently projected on the skin through pressure) a cosmetic product? Answer: The moistened picture may be considered as a preparation. It is intended to be placed in contact with the skin in order to change its appearance.   Therefore, such a product is considered as cosmetic product

TYPE OF PRODUCT – Ingestion-tablet” Question: Is a product to mask bad breath which presents itself as tablet to be dissolved in the saliva and which is ultimately swallowed a cosmetic product? Answer: Cosmetic products are defined as intended to be placed in contact with the various external parts of the human body, and not to be swallowed Therefore, it is considered as “borderline” products between “cosmetic product” and “food”. The product Must meet the requirement of both food & cosmetic

TYPE OF PRODUCT – Ingestion- chewing gum Question: Is a product to keep teeth clean or to reduce bad breath which presents itself as a chewing gum a cosmetic product? Answer: A chewing gum consists of a gum base (acting as a "vehicle") which releases substances and/or preparations in the mouth while it is chewed to reduce bad breath, therefore, it meets definition of a cosmetic products, and since it is ingested it is considered as borderline cosmetic with food. But if the substance/substances has a medicinal effect then, it is considered borderline cosmetic with drug.

TYPE OF PRODUCT –Borederline with Biocides - Leave-on products presented as “antiseptic” or “antibacterial” Question: Is a leave-on product which, according to its presentation, is a mask with an “antiseptic” or “antibacterial” a cosmetic product? Answer: A product which presents itself as a cosmetic product being mask, and has an “antiseptic” or “antibacterial” may be a biocidal product, (borderline a cosmetic product with a medicinal product. With regard to the “borderline” cosmetic products/biocidal products as defined in the Biocidal products.

TYPE OF PRODUCT – "Antiseptic" or "Anti-bacterial" Mouthwash ” Question: Is a mouthwash which, according to its presentation, is “antiseptic” or “antibacterial” a cosmetic product? since it is intended to be placed in contact with the teeth and the mucous membranes of the oral cavity to clean, perfume them, then it is cosmetics product as well. Answer: A mouthwash which presents "antibacterial" or "antiseptic" claims can be qualified as, a biocidal product – with a medicinal product.

TYPE OF PRODUCT – "Antiseptic" or "Anti-bacterial" Mouthwash ” Question: Is a product containing substances which restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action a cosmetic product? Answer: If a product is a medicinal product, it falls exclusively within the regulatory framework of medicinal products. A product can be a medicinal product ‘by virtue of its presentation’ or ‘by virtue of function’.

TYPE OF PRODUCT – Nasal sprays Question: Are nasal sprays cosmetics products? Answer: No, nasal sprays are not cosmetic products due to their place of application. The definition of cosmetic products covers "any substance or mixture intended to be placed in contact with the external parts of the human body. The mucous membranes of the nasal cavity are not covered in cosmetics. Pharma & Cosmetics in the GCC Region

TYPE OF PRODUCT –products containing substances stimulating hair growth or reducing hair loss cosmetic products ” Question: Are products containing substances stimulating hair growth or reducing hair loss cosmetic products? ” Answer: this product or its substance(s) restores, corrects or modifies physiological functions by exerting a pharmacological, immunological or metabolic action, then it qualified for medicinal product. Also, since it is intended to be placed in contact with the external parts of the human body & has beautifying effect, it is qualified for a cosmetic product. Therefore, it must meet both product requirements. Pharma & Cosmetics in the GCC Region

TYPE OF PRODUCT – " Borderline with medicinal Products ” Question: Question: Is a product which, according to its presentation, is intended to exclusively or mainly relieve joint pain, a cosmetic product? Answer: The principal purpose of a cosmetic product is defined by the Cosmetics Regulation as “cleaning”, “perfuming”, “changing the appearance”, “correcting body odors”, “protecting”, or “keeping in good condition”. It not a cosmetic product. Pharma & Cosmetics in the GCC Region

Products delivered through iontophoresis or similar mechanisms Question: Can products specifically intended to be delivered through iontophoresis or similar mechanisms be cosmetic products? Answer: Iontophoresis and similar mechanisms are techniques .Such techniques could be used for cosmetic purposes. If the use of device only results in a superficial penetration of the product in the epidermis, then the product is a cosmetic and its safety should be assessed taking into account this mode of delivery. On the other hand, if the use of device induces a deeper penetration of certain ingredients, then the product could not be qualified as a cosmetic, but as medicinal. Pharma & Cosmetics in the GCC Region

Skin-whitening products Question: Are skin-whitening products cosmetic products? Answer: yes, in principle skin-whitening is considered as a cosmetic purposes such as beautifying effect & promoting attractiveness. However, pigmentation disorders, such as melasma, chloasma and lentigo, are considered as medical conditions, and products intended to treat them fall in the scope of the Medicinal Products legislation. Pharma & Cosmetics in the GCC Region

Topical products to relieve tired, swollen or heavy legs Question: Are topical products to relieve tired, swollen or heavy legs cosmetic products? Answer: No, leave-on products presented as relieving tired, swollen or heavy legs are treating minor peripheral circulatory disorders and therefore cannot be qualified as cosmetics, but as medicinal products. But if the products have cosmetic function as refreshing, cooling, soothing for the legs could be qualified as cosmetic products, Pharma & Cosmetics in the GCC Region

Anti-wrinkle products Question: Question: Are anti-wrinkle products cosmetic products? Answer: Yes, in principle anti-wrinkle products promote attractiveness can be cosmetic products However, some products presented as anti-wrinkle may significantly restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action. In that case, they would not qualify as cosmetics, but as medicinals. Pharma & Cosmetics in the GCC Region

Product to treat dry mouth Question: Are products to treat dry mouth cosmetic products? Answer: Products to treat dry mouth act by stimulating the production of saliva. This mode of action is not compatible with a cosmetic function; therefore, they are not cosmetic products. They are qualified as medicinal product. Pharma & Cosmetics in the GCC Region

Safety/Toxicity Raised Concerns Section IV Safety/Toxicity Raised Concerns

Concerns -Oxidative hair dyes The following current safety/exposure risk/toxicity issues are of concern.   Oxidative hair dyes contain arylamines, the most chemically reactive ingredients of cosmetics. In previous studied it was reported that an association of oxidative hair dye use and increased bladder cancer risk in consumers. Recently the results suggest that modern hair dyes and their ingredients pose no genotoxic, carcinogenic or reproductive risk. Pharma & Cosmetics in the GCC Region

Concerns- Ultraviolet filters Ultraviolet filters have important benefits by protecting the consumer against adverse effects of UV radiation; These substances undergo a stringent safety evaluation under current international regulations prior to their marketing. Concerns were also raised about the safety of solid nanoparticles in cosmetics, mainly TiO2 and ZnO in sunscreens. However, current evidence suggests that these particles are non-toxic, do not penetrate into or through normal or compromised human skin and, therefore, pose no risk to human health Pharma & Cosmetics in the GCC Region

Metal Oxide Nanoparticles Metal oxides, such as TiO2 and ZnO, are found in many commercial applications

Concerns- natural plant ingredients The increasing use of natural plant ingredients in cosmetics and cosmeceutical products . Novel approaches to their safety evaluation similar to those of plant-derived food ingredients. For example, the Threshold of Toxicological Concern (TTC) is a promising tool to assess the safety of substances present at trace levels, Minor ingredients of plant-derived substances. Pharma & Cosmetics in the GCC Region

Conclusion/ cosmetics safety issues Overall, today's safety assessment of cosmetics and their ingredients is not only based on: Science, Respective regulatory status The ethics of animal testing. Nevertheless, the record shows that today's cosmetics are safe and offer multiple benefits to quality of life and health of the consumer. Stakeholders, consumers, regulatory bodies and producers, are waiting for an international harmonization on the status. Pharma & Cosmetics in the GCC Region

Concerns- in vitro skin penetration The potential human systemic exposure to cosmetics ingredients is increasingly estimated on the basis of in vitro skin penetration data. However, new evidence suggests that the in vitro test may overestimate human systemic exposure to cosmetics ingredients due to the absence of metabolism in cadaver skin. Therefore, alternative methods now are going on. Pharma & Cosmetics in the GCC Region