Education Articles

Clinical Study Dos and Don’ts:  Designing Safety & Claim Support Studies

Nothing makes an R&D director happier than providing a validated sound scientific dossier to his/her marketing team on a technology or formulation that has gone through months, if not years, of development.  From inception to market, there are endless meetings about progress, budgets, resource allocation and most of all, data generation.   When you think about all of the time and energy you have spent on this one aspect of your pipeline, validating your work becomes paramount so that it is universally accepted by not only the market place but by your management and investors as well. Ironically, this is the most crucial and usually the most expensive point of the project as a whole.  What can you do to ensure that you are efficient in your success?

In order to properly validate your mechanism of action and support your claims, an outside lab is usually brought into the fray for good reason: you want an objective 3^rd party verification of all you have done to this point.   This will entail having all of your project management skills ready to go. This is akin to getting to the championship game in your favorite sport.  The whole season now rides on how well you do in the next game or series.  How do you position yourself for success?  Below you will find some do’s and don’ts that I have been faced with, both as a client and as a provider of clinical testing for personal care and cosmetic products.

Are you Ready to Test?

From the service side of the industry, I find that many clients come to the table thinking they are ready to test with a 3rd party laboratory. However, after the first meeting is over, they are usually going home with a to-do list longer than the questions they had for me.  So, ask yourself, are we ready to test?  No matter your title or level of responsibility, you must build a team to answer this question.  Having a team in place that represents all facets of the project, including where you have been and where you are going is the first step.  Understanding how you landed on the functional claims, category and target consumer/customer are going to lay the foundation of what type of 3^rd party lab you will need and what type of study design is warranted, as not all testing labs are created equal.  All of your team members must bring their information and needs to the table to answer that question before you pick up the phone and ask for 3rd party commitment.  Have a timeline built and map out the approval process commensurate with your company’s policies.  There are some companies that inherently have more red tape than others.  Know and understand your internal process before bringing in outside counsel.  This will certainly convey confidence and keep you in the driver’s seat.

Represent your Stake Holders

Having a good mix of representation on your team of R&D, marketing, operations, regulatory and sales personnel, especially in the initial meetings with a 3^rd party laboratory, will ensure that everyone’s needs are accounted for and visible.  This will also make for a much smoother utilization of data when it comes time to launch.  Some of the best launches are the result of this synergy alone.

Communication

Gathering, moving and analyzing information is the norm in today’s market place and is critical for success.  It is imperative that the team you build have an open channel of communication within its team members and the lab when necessary.  As the team leader/project champion, you must know who your go-to people are.   There are often cases of misplaced assumptions regarding who knows what, and who is responsible for deliverables and decisions.  Many times I work with a project team looking to perform validation studies only to find that delays are imposed from executing as planned because the test materials are not available or not delivered on time to the testing facility.  There are many reasons for this.  Some examples include delays in release from QA, test materials that have not passed physical or chemical stability, last minute changes to the formulation design and for our international clients, test materials getting stuck in customs at the border.  All of these issues can be mitigated with proper channels of information being open.  If one person is the gate keeper of all the information, that person needs to have access to all facets of the project and to includes information that the team members possess.  Establishing portals for information sharing especially when collaborations exist over multiple time zones is something to also consider. At the end of the day, proper, concise and efficient communication is paramount to keeping all stakeholders informed and abreast of the status of your project.

Understand your Goals

Have a holistic view of the expectations and goals.  I always say to prospective clients, “work your project backwards”.  Assuming that you get the best data possible, what will you say about it?  Understanding the end game allows everyone to see the goal in the detail that is needed.  Having a vague undefined goal is grounds for confusion, uncertainty and delays to market.  Having the goal in mind is also crucial for developing the protocol to get you to the desired objective.  One of the most common delays and unpredicted expenses companies incur are due to last minute protocol changes.  These cause delays in final approvals, delays in recruiting the required subjects, and ultimately delays in study execution at the 3^rd party lab. There is a high risk for decisions being made before final protocols are signed by not having your team review the protocols early on. This can lead to re-works, delays and loss of access to resources, equipment and personnel needed to perform the study.

Know your Financial Limitations

Budget, budget, budget, how many times have we all heard, “we can’t do that, it’s too expensive”?  Have a deliberate budget in mind when you are ready to validate claims.  You can start off shooting for the stars but inevitably, you land back on earth holding your budget in hand saying, “we need a new plan”.  Match your needs within your budget.  So many clients come to me with a beautiful study design only to realize that it is light years beyond what they budgeted for.  Factors that drive price in any clinical study are of course the time and resources allocated by the lab; however, there are study design oversights that drive up study costs significantly.  Having time points that can be managed Monday through Friday and within a regular work day reduces overtime commitment by the lab.  Choosing technicians (or expert graders) to perform evaluations other rather than MD’s (where appropriate) is another way to save money.  IRB cost, interim data requests, expedited reports and last minute changes to the schedule once protocols are signed are huge drivers of cost, and many of these can be avoided with proper planning and good team building.

Focus on what you want to Achieve

Validation of claims or target mechanism of action is in the eyes of the beholder.  Keep in mind, in the personal care industry, consumer perception trumps all.  If your technology/finished product does not deliver on consumer perceivable results, you most likely will not get a return customer and the market will quickly lose interest in your product.  The good news is, consumer use studies are not that expensive.  Know your consumer base, ask the right questions and provide the best use instructions possible.  Many clients like to marry consumer use data with objective instrumental measures and/or expert grading.  This is the trifecta of clinical study success.  If you can show agreement with consumer perception, instrumental measures and expert assessment, you have a solid foundation for a bullet proof marketing campaign.

Understand your Consumer

Consider the consumer experience when designing your study.  Have you prepared use instructions that best represent how the product will be used?  Do you have a mechanism in place to understand off indication used of your product?  Factoring in these questions is critical to reduce the variation in consumer generated data.  People in general are variable in their recollection of experiences.  Having a way to reduce this through easy to read, easy to understand, and simple use instructions makes for a happy experience.  Consumers/subjects evaluating a product will, when asked, provide valuable negative feedback as well.  Ask for it, don’t wait for it.  It’s better to understand the short comings of using your product before it hits the market.  Is your product providing comfort and ease of use?  If so, it will be viewed in a better light.  Ask for diary comments, proof of use, have a hot line into the testing company for adverse event reporting.  All of these provide subjects on your study with a positive experience which will ultimately be reflected in your data on product performance.

Translate your Science and Check Regulatory Requirements

Marketing should play an integral role as a co-champion of the validation process.  They should be able to translate the science to consumer language which in turn should be converted to questions used for consumer perception studies.  Marketing should also understand what the competition in their particular category is saying about similar products.  3^rd party labs do not make marketing claims; they provide data to support them.  Your marketing team should also have a hot line to a regulatory expert in the geographic regions of where you plan to sell your product.  So much for world harmonization, the individual regulatory requirements worldwide are ever growing further apart and complex.  Don’t spend your valuable time and resources developing a technology only to find out you can’t sell it in your target region because of regulatory hurdles, restrictions on trade, and/or miss alignment with what is culturally acceptable.

Know your Data

Finally, what to do with your data?  Chances are, you may be in charge of getting a 3^rd party laboratory to perform some validation or claim support studies but you don’t remember the first thing about statistics.  Your report comes back from the lab with P values and Z scores.  Paragraphs about significant and non-significant data along with ANOVA analysis….YIKES!, what does all of this mean?

Did you set up the study to have the data be understandable or are you counting on one of your science team members to make sense of it all?  Is the data audited?  So many times as a client, I have asked for the raw data to review and “crunch” myself to better understand the relationships.  On the flip side, as a testing lab, I have had clients spend significant time and money on a study and not know what their data means or how to apply it back to the original objective of the study.

Final Remarks

No matter how you get to your goal, always keep in mind the fundamentals.  They are so easy to take for granted and in retrospect, the lack of attention to the fundamentals is the very reason why projects don’t go as planned.  So, build an effective and comprehensive team, know your budget limitation upfront, manage information in and out of the team efficiently, understand the expectations and stick to the plan. Understand the needs of your customers and translate the data in a way they understand.  Last but not least, know your market and consumer front to back and translate data so that they both understand it to the point at which they come back for more.

Author’s Biography:

Michael Anthonavage is the current VP of Operations and Technology at Eurofins CRL Cosmetic Testing. Michael has 20+ years of experience in personal care product development and a career spanning background in skin biology and models and methods development. He specializes in R&D to marketing translation and claims validation, both in vitro and in vivo. Michael is an engaging public speaker and product technology advocate with an ability to marry complex ideas and concepts to various consumer needs; he is also an educator in the area of herbal studies, instructing students in the study of plant chemistry and their impact on human physiology.  Michael has a number publications and patents to his name and continues to be an influential speaker in personal care, bioinstrumentation and skin testing.

Solar Ultraviolet Radiations UVA and UVB are complete carcinogens. They both cause DNA damage and, in the process of DNA repair, mutations are generated at non-negligible rates. Some mutations provoke the so-called transformation in which a cell acquires unlimited replication potential and loss of growth control.

UV radiation is also known to be the single most effective factor of skin aging. This occurs via the elicitation of a strong inflammatory reaction that provokes multiple oxidative cascades as well as the release of Matrix Metallo Proteinases, the consequent disorganization of the elastic fibers and a massive deposition of elastin.

Since the early twentieth century it is known that sunburn is provoked by UVB and the cosmetic industry developed UVB filters to protect against it. For two generations, between 1935 and 1985, UVB filters were used to protect the skin. In spite of the use of these filters it was observed that the skin of sun-worshippers became sagging and accumulated wrinkles, as if something else than UVB could accelerate skin aging. Experiments performed in the late 80s and early 90s by casting UV radiation of defined wavelengths on the skin of hairless rodents allowed scientists to realize that skin sagging is the consequence of UVA irradiation (1). UVA was also shown to induce DNA damage when in the presence of Oxygen and transition metals (2), as is the case in vivo. The cosmetic industry therefore developed UVA filters.

The preparations of formulas to protect against UV radiation is not straightforward, insofar as the protection afforded by the filters is not proportional to their concentration, that is that in order to double the SPF of a formula one might need to increase the concentration of the filter by a factor of three or four, and the filters at high concentration affect the esthetics of the formula and might affect the health of the skin as well. In addition, the UVA filters agreed to be in the positive list of the FDA are unstable. Remarkably, the FDA opposes the addition to the positive list, of new, stable UVA filters that transfer energy to molecular Oxygen and produce singlet Oxygen, the most reactive of the Reactive Oxygen Species. The FDA is probably right: with Quantum Yields of singlet Oxygen generation that reach up to 0.09, these UVA sun-filters could safely be called photosensitizers.

There is a need for new, safe, non-expensive UVA filters. They can be found in nature, for instance as components of edible algae (3). Plants and algae are particularly interesting insofar as they are accessible to investigation and constitute a sustainable material for extraction or production. Porphyra umbilicalis (also known as Nori) is an alga growing on Asian coastal lines. It is used to wrap sushi pieces in Japanese cuisine. It contains relevant amounts of Mycosporine–like amino acids (MAA) which absorb UV radiation with a sharp peak in the UV-A region, centered at 334 nm. Its molecular weight is around 350 and its molar extinction coefficient at 334 nm is 44,000. This is to say that its K-value is similar to the one of Parsol 1789. Nori extracts can be used to dramatically improve the broad-spectrum absorption of sunscreens. Materials absorbing at 330-340 nm are also demanded globally, for products aimed at evening skin tone, because they absorb in the UV-A region known to provoke the immediate pigment darkening.

Oftentimes the process of extraction of the material of interest only offers a limited yield, as it is the case when the material of interest is unstable in the conditions of the extraction, but this is not the case for the MAA from Nori. The biomass is suspended and incubated in diluted acetic acid (~0.5%) (1:50 w/v) to avoid the extraction of large cellular polymers such as DNA and RNA. Upon separating the biomass from the extraction fluid, a second round of extraction and possibly a third round of extraction can be performed, so as to extract as much of the molecule of interest as possible, when this is compatible of the cost of the extraction itself. The extraction fluid is then concentrated and reduced to a powder state by the process of Spray-drying.

At this stage the extract is appropriate for being used in cosmetic formulas. The cost of extraction is minimal and the abundance of the biomass is such that the cost of the bulk of algae is negligible. This makes the MAA from Porphyra umbilicalis an ingredient of choice for new sunscreens. As a matter of fact, this MAA does not absorb in the UVB and as such, technically, it is not considered to be a sun-filter by the FDA and can therefore be used to boost the protection of broad-spectrum sunscreens.

References

1- Bissett DL, Hannon DP, Orr TV (1989) Wavelength dependence of histological, physical and visisble changes in chronically UV-irradiated hairless mouse skin. Photochem Photobiol 50 : 763-769

2-Audic A, Giacomoni PU (1993) DNA nicking by UV radiation is enhanced in the presence of Iron and Oxygen. Photochem Photobiol 57 : 508-512

3-Sinha RP, Singh SP, Häder DP (2007) Database on mycosporine and mycosporine- like amino acids (MAAs) in fungi, cyanobacteria, macroalgae, phytoplankton and animals. J Photochem Photobiol B 89 : 29-35

Paolo Giacomoni acts as an independent consultant to the Skin Care industry.  He has served as CSO of Élan Rose International (2015-2-2018), as VP of Skin Care R&D with Herbalife (2011-2014) and was Executive Director of Research at Estée Lauder (1998-2011). Dr. Giacomoni was also in charge of research and communications for Clinique and has conducted research on cell and surface biochemistry for best-selling products.  During his tenure at L’Oréal, as Head of the Department of Biology, and then as scientific attaché to the Director of Applied Research, he built a record of achievement through research on DNA damage and metabolic impairment induced by UV radiation as well as on the positive effects of antioxidants.  Dr, Giacomoni was one of the founders of the European Society for Photobiology as well as of the European Network for the Study of the Biology of Aging. He has authored 100+ publications and patents. He received his Ph.D., in Biochemistry from Université Paris VI, a Laurea in Atomic Physics from Università di Milano, and had Post-Doctoral Training at Deutsches Krebsforschungszentrum, Heidelberg, at University of Wisconsin, Madison, WI and at University of California, San Diego, CA.

As a skin biologist and researcher of technology in the personal care field for over 20 years, there are few times in one’s career that you experience a trend that has the legs to become a new playing field in science.  The skin microbiome strides made in recent years have truly been remarkable.  Not only have the number of products available addressing the skin microbiome exploded but the number of research papers and articles on the topic has captivated the industry.  Furthermore, it highlights the direction and utilization of systems biology as a tool by applying the learnings of microbiology, skin biology, biochemistry, genetics and ecology all into one discipline.  The field is still in its infancy and in constant transition as the methods and models being employed are still being optimized to reduce bias and improve precision and accuracy.

The single primary driver of this new frontier are the remarkable advancements in high throughput gene sequencing and the computational analysis required to handle massive amounts of data and put it into a meaningful perspective.  Not only can we identify bacteria faster and more cost efficiently, but now we understand through genetic comparisons that strains of a species can differ significantly resulting in the difference between health and disease under a variety of conditions.  This was one of many topics permeating throughout a recent scientific microbiome congress held in Boston pulling together forces within the industry to form a multi-disciplinary approach to the opportunities and advancements within this growing field.   Other topics included consumer education, regulatory preambles, biological target identification, microbiome relevance, host-biome interactions and advances in technology used to study the human microbiome.

With all science comes controversy.  Areas of debate range from what defines a healthy microbiome to how diverse the microbiome should be and why our skin is losing its biodiversity.  Many claims and research point to our forefathers (hunter gatherer societies today) as having a much more diverse skin microbiome than modern man.  Thus, the prevalence of skin-related issues is markedly reduced in tribes living in the Amazon compared to that of our modern city dweller.  This loss of biodiversity has been linked to a significant increase in allergy-related disease.  Furthermore, the use of preservatives and complex ingredients in skin care products has been deemed suspect.  The relevance to other trendy areas within skin care can now be woven with a new perspective.  These include the role of pollution and the duration of solar radiation exposure.  Since the skin is the youngest organ in our body in terms of evolution, the sun and atmospheric environment plays a major role in its phenotype and function.  Research is now linking the evolution of our skin microbiome to the same influential environmental pressures.

The skin microbiome is the total sum of all microbes that live on or in the skin.  It is a highly dynamic entity that is analogous to a beehive in that it is responsive and adaptive to the many internal and external factors influencing its environment all simultaneously.  The exciting aspect of the skin microbiome is that it will force traditional science to think differently.  Application of environmental science theorems are now being placed into equations, hypotheses,  and experimental designs previously limited to a classical reductionist algorithm that one needs to understand the parts before understanding the whole.  This modality of scientific exploration has been dominated by the study of molecules explaining cells which, in turn, explains the function of tissues and helps us to understand how organs work and interact with in systems.

This is just part of the story.  Moving forward, we now must consider levels of organization that typically ended with an understanding of our own species.  With the skin microbiome, we need to consider the fundamentals of science from a more complex standpoint.  For instance, a full understanding of strain introduction within a species, population diversity with in specific organs, and communities of microbes between body sites are now combined with our classical understanding of skin biology to explain how this entire ecosystem influences our day to day function, health, and disease.  Truly, a new frontier awaits us.   I guess this is what the explorers Louis and Clark felt like starting their journey to the Pacific Ocean.

So where are we in this journey?  Researchers have characterized the human skin microbiome as both functional and site specific as it pertains to different regions on the body.  The two most distinct body environments are those with sebum and those without.  Compounding these areas are those under humidity, occlusion, and moisture and those that are not.  Of course, there are other microclimates on or in our skin including the follicular surface areas of hair, sweat and eccrine glands.  Understanding how each of these microclimates works at different stages of life, within ethnic groups, different geographical locations, and between the sexes is just the tip of the iceberg.

Areas of the skin that are rich in sebum have garnished much attention as these areas are most prone to acne as illustrated in work done by Prouty and Pappas.  It is within this area that we see some very interesting correlations with our skin actually regulating its own biodiversity.  Hair follicle-associated sebaceous glands secrete sebum, a highly complex lipid mixture that covers the skin surface and hair shafts. The functional versatility of lipids, combined with the wide array of sebaceous lipid classes, provide skin with a substrate that facilitates adaptation to diverse environmental situations, including interactions with microbes.  Analysis of sebum and its components have shown that a particular specific fatty acid called sapienic acid (16:1 n10), has been shown to be antimicrobial to Staphylococcus Aureus, the very species implicated in flare reactions in atopic dermatitis.  Furthermore, infection by Staphylococcus aureus is associated with a reduction in sapienic acid in the sebum of patients with atopic dermatitis, and topical application of sapienic acid is correlated with decreased bacterial load and reduction of symptoms. Taken together, this strongly suggests that sapienic acid functions as a “first-line” component of the innate immune system at the skin’s surface.

The beauty of this great journey is that it may explain and give way to an entirely new approach to skin care.  Host-biome interactions will be the focus of healthy immune development from birth to treating maladies such as atopic dermatitis, rosacea, acne, and dandruff, and body odor.  Learnings from the skin microbiome are migrating into oral and vaginal health arenas, changing the way we look at health and disease as well.

While research scientists unravel the complexities of the skin microbiome, the interest from within the industry is also buzzing with discovery and innovation.  There seems to be multiple avenues to enter this space and all have shown some level of promise in terms of delivering on claims.  We can certainly thank the yogurt industry for laying the ground work with the consumers.  From study data presented in Boston, consumers (especially Millennials) seem to get the concept of taking care of your skin the same way you take care of your gut microbiome.  Although, most consumers have a rudimentary understanding of microbiome, they are very willing to try products targeting it.  Reinforcing a healthier lifestyle, conforming to more natural-based hygiene practice or looking to change the way their skin behaves is all the motivation consumers need.

New technologies and innovation are taking form in a variety of ways.  Prebiotics seem to be gaining the most momentum in skin care as evidenced by the number of new prebiotic technology offerings seen at the last two In-Cosmetics shows. Prebiotics are those materials that feed, nourish, and/or manage the skin microbiome in some form or fashion.  Examples of prebiotics are polysaccharides, polyols, free fatty acids, fibers nitrogen sources, and lactic acid.  By focusing on prebiotics, many technology companies avoid the complexities of having to grow live cultures of bacteria to generate a second category called probiotics.  With this strategy, we see the use of live bacteria whether sourced from skin or other substrates like soil.  Some are using the very bugs found in yogurt while others are applying species said to be part of our microbiome during earlier times of human existence but were lost.

This category of products is the most complex and wrought with controversy.  Should live or dead microbes be used?  How do skin bacterial communities change with new species introduction?  How much biodiversity is too much?  All of these questions are being studied at every level of complexity.  Another branch of probiotics is now emerging by genetically engineering normal flora strains to secrete enzymes and factors needed to correct deficiencies in skin physiology.  A well-known condition called atopic dermatitis is characterized by inflammation, itch, a reduction in barrier function, and loss of moisturization.  Researchers are now programing Staphylococcus epidermidis, a commensal microbe (found to be reduced in atopic dermatitis) to secrete barrier-related proteins, enzymes to increase lipids, and antimicrobial peptides to reduce the Staph aureus load (which supersedes that of Staphylococcus epidermidis in atopic dermatitis).  Lastly, we have the category of postbiotics.  This group consists of fermentation products and supernatants from bacterial culture.  These materials are the next generation prebiotics.  Designed and targeted to shift to better microbiome health, an increase in biodiversity, and to provide a new way to achieve clean healthy beauty.

The journey to understanding the skin microbiome is well underway.  Nobody knows for sure where we will be in the next 5 to 10 years. The models and methods used to study the skin will advance and become more sophisticated as well, as the products and claims associated with these new discoveries develops.  It is exciting to see so many disciplines coming together to unravel the mysteries of our microbial populations and communities living and working with us in so many ways.  New levels of understanding will be achieved in exploring commensal and symbiotic relationships with our tiny friends.  The skin microbiome field will inevitably fall into sub-specialties where you have the folks looking to keep skin clean and free of microbes while others will look to preserve and propagate the populations of beneficial microbes to sustain and promote healthy skin. When it comes to research into the skin microbiome, we truly are the sum of all of our parts and then some.

Michael Anthonavage has 20+ years of experience in personal care product development and a career spanning background in skin biology. Michael has extensive knowledge in product development in the area of personal care product design and specializes in R&D to marketing translation. He is an engaging public speaker and product technology advocate with an ability to marry complex ideas and concepts to various consumer needs. Michael is currently the Director of Advanced Clinical Services at CRL. Michael’s previous positions involved R&D leadership positions at Johnson & Johnson Consumer Products, Presperse and Vantage Specialty Chemicals.  Michael is currently on the NYCSCC Scientific Advisory Board and has a number publications and patents to his name.

Muslims around the world used the word Halal for many years to describe a certain dietary regimen. The roots of the word originate from the Quran and Shariah and it typically defines how animals are slaughtered and restricts the consumption of certain animals, and alcohol.  In general, everything created by God is allowed as food with some exceptions.  These exceptions include pork, blood, animal meat that was not properly slaughtered, alcohol, intoxicants, and inappropriately used drugs.  With regard to fish, all fish with scales are allowed but animals that live both in water and on land like frogs are not allowed.  In addition to previously described restrictions, Genetically Modified Organism (GMO) and body parts/fluids are not allowed.  For example, gelatin is not considered Halal if it comes from pigs or from animals that were not slaughtered properly.  Keratin and stem cells from human origin are not allowed as well.

In the last decade, the word Halal was used to describe not only foods but also personal care products as well as cosmetics and a variety of other marketed products. The demand for Halal products has continuously grown over the past few years and is expected to grow even further.  For cosmetics, raw materials as well as finished products are subject to certification.  As a general rule, during the Halal certification process the products should first meet all local guidelines in terms of safety purity and quality.  For example, if the product is under the FDA jurisdiction, it must meet first such guidelines and then be considered for Halal certification.  The certification process typically starts with an application, followed by submission of the documents related to sourcing of all raw materials and is typically finalized with an onsite inspection.  The onsite inspection considers factors like manufacturing, storage, packaging and transportation of such products.

In North America there are several agencies that certify raw materials and cosmetics products. The Halal Advisory group www.halaladvisory.com is one of such agencies and is located in New York city. Another agency of interest is the Islamic Society of the Washington Area known as ISWA www.ushalalcertification.com. This agency is located in Washington DC and like other agencies has an online application.  The Islamic Food and Natural Council of America (IFANCA) is located in Park Ridge, IL and has a web presence at www.IFANCA.org the agency grants Halal certificates as well. For European companies, The Muslim Food Board (TMFB) located in the United Kingdom issues Halal certificates under its division; Halal Certification Europe.  Applications can be submitted online at www.tmfb.com.

I hope this short synopsis will give the reader an overview of the Halal guidelines, and means to obtain certification for raw materials and finished goods. If additional information is needed to understand the Halal standards, one good resource is The Malaysian Standard MS 2200 Pat1: 2008 which describes the practical guidelines for handling Halal cosmetics.

Dr. Hani Fares started his career in personal care studying the effect of solvents on sunscreen chemicals. His interest in skin drug delivery especially from polymeric matrices grew during his graduate work at Rutgers, where he completed his Ph. D. in Pharmaceutics. Dr. Fares worked at Block Drug and GlaxoSmithKline where he held positions in research and development in the areas of skincare and oral care.  After that, he joined L’Oreal where he held several positions of increasing responsibility leading to AVP of skincare.  He is currently the Senior Director of skincare and oral care at Ashland Specialty Ingredients.  Dr. Fares is the author of many publications, and patents and made many presentations in national and international meetings in the areas of suncare, skincare, and oral care.

In 2018 the modern fragrance industry will focus on technology, the regulatory environment, and the creative challenges. One of the hottest topics and trends outside of these specific focuses in not just fragrance but all of cosmetics, industrially or independently created, is natural products and formulation, and one that has triggered a wide variety of dialogues and raises many questions for both consumers and producers.

Before recently, one would have to build a time machine to find a bottle of Kyphi, an Ancient Egyptian incense or wearable perfume thought to be a blend of cassia, cinnamon, mastic, mint, henna, and mimosa in a medium made from honey, wine, and raisins (though the precise formulation is subject to scholarly debate and varies). Now, you just have to contact a ‘natural perfumer’, many of whom operate on web-based commerce platforms and have built their businesses online through social media – a common gathering place for those who share similar opinions on the natural trend.

Many of these natural perfumers will advertise that their perfumes are composed using essential oils and absolutes as sources of fragrant compounds that have been ‘naturally’ obtained through steam distillation, tincturing, effleurage, hexane-free extractions, and so on. This would be in contrast to ‘synthetic’ compounds that are synthesized in a laboratory from other chemicals, some of which are not found in nature and so can only be produced by these methods.

But why is ‘natural’ so popular, and marketing based around ‘natural’ products so effective lately? It is because consumers are far more invested in their health and wellness as well as the health and wellness of the environment, which is a fair concern as both could potentially be impacted by the fragrance industry, as exemplified by studies on how some older synthetic musks could harm the defense systems of marine life¹ and an increase in sensitivities to fragrances noted by the American Academy of Dermatology.²

However, I am not here to espouse the idea that ‘natural’ ingredients and products are a way of the future, even though naturalism has been an effective tool of marketing in order to capture an emerging niche in the cosmetics and fragrance market, nor am I here to indict any synthetic materials as potentially harmful. Instead, I wish to raise questions as to the validity of natural-synthetic dialectic, on which discussions around safety seem to be based amongst consumers of fragrances whether natural or synthetic or anywhere in between, when the line between ‘natural’ and ‘synthetic’ is becoming more and more blurred.

The ultimate catalyst for that blurring is the biochemists and bioengineers who have worked to develop cutting edge biosynthetic methods of producing fragrant compounds. This involves introducing novel, artificially designed genes into the genome of bacteria, which when provided the right starting materials will synthesize and produce fragrant chemical compounds, or utilizing enzymes which are able to perform a specific transformation.

Akigalawood, a captive ingredient of Givaudan’s, was produced utilizing the latter method. Their Biosciences Team found that the enzyme laccase, with processing using just water and salts, was able to transform a natural material into a new fragrant compound, never before available to perfumers and having profile similar to patchouli with hints of spicy pepper and agarwood. The former approach has seen much use as well, an example being Ginkgo Bioworks of Boston, MA having worked with Firmenich to engineer yeast capable of producing a complex mixture containing the compounds found in rose essential oil.

These developments make mince-meat of once common semantics and raise many questions that should be answered in the coming future. Is Akigalawood a ‘natural’ material if it was produced by an organism and not by chemical synthesis? Is linalool isolated from lavender oil by distillation ‘synthetic’, as it was produced using laboratory equipment? The discussion of what can be categorized as natural or synthetic by the consumer becomes quite complex once these considerations are made.

Further complicating the consumer discussion of safety and environmental friendliness is the fact that that ‘natural’ is not always better for the industry, consumer, and environment, counter to the ‘naturalistic fallacy’ which is the reason the trend for ‘natural’ cosmetics has seen the expansion it has. For example, sassafras oil is carcinogenic, the high levels of ketones present in sage oil are toxic, and furocoumarins in bergamot oil and atranol and chloroatranol in oakmoss absolute can cause skin reactions if not removed through laboratory processing.

Additionally, a consumer who fancies strongly rose-tinted glasses may also believe that natural materials are better for the environment, which is not necessarily true. Over-sourcing of sandalwood rosewood and agarwood has led to them becoming endangered and near extinction, and tragically the musk deer was hunted to near extinction for its musk pods to use as a natural perfumery material in the past.

In the eyes of IFRA, the regulatory body overseeing the safety standards and proper usage and amount recommendations for fragrance materials in cosmetics, it does not matter whether the material is natural or synthetic, as there are plenty of materials that are available only through chemical synthesis on their restrictions – it only matters to them whether it is safe, which is I believe the proper semantic framework to discuss ingredients and formulation for both the industry and especially the consumer, not the natural-synthetic dialectic brought about by consumer trends.

If anything, these misperceptions and trends founded on a now shaky dialectic and not overall safety signify that there is much work to be done on the relationship between company, consumer, and the environment. I believe firmly the focus of that relationship should be safety, transparency, and most importantly sustainability, rather than on the semantic category of the materials used in a formulation. Moving forward into the future of fragrance science, it should not matter whether a material falls into a certain category, but rather that it is safe for humans, animals, and the environment, and thankfully it appears we are moving in that direction. Finally, if there is an overwhelmingly positive aspect to the naturals trend, it is that it has sparked this discussion, and for that there should be gratitude.

References:

1. Schwartz, M. 2004. Household fragrances may be harming aquatic wildlife, study finds. Stanford Report. Retrieved from https://news.stanford.edu/news/2004/november3/Perfume-1103.html
2. Bouchez, C. Fragrance Allergies: A Sensory Assault. Retrieved from https://www.webmd.com/allergies/features/fragrance-allergies-a-sensory-assault#1

Matthew Brooks, Boston University, B.A. Chemistry 2019. A third-year student of chemistry at Boston University and fragrance consultant at Sephora, Matthew plans to enter the cosmetic industry upon graduation, where he hopes to work in product development and formulation. His recent areas of interest and study include natural products and organic chemistry, polymers and raw materials, ‘green’ chemistry, sustainability, and environmental protection.