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Skin Care Products:
Claim Substantiation & Clinical Testing
Barbara Dvoracek
Senior Research Scientist
Kimberly-Clark Corporation
Benedictine University
Cosmetic Chemistry
November 13, 2007
Personal Background
• M.S. in Microbiology: University of Wisconsin – Oshkosh
• Employed at Kimberly-Clark Corporation since 2000
• Skin Science Research
– 2000 - 2004
• Research Scientist
– 2004 - Present
• Clinical Study Coordinator
• Team Product Safety & Regulatory Affairs liaison
Regulation of Skin Care Claims in US
• Food & Drug Administration (FDA)
– Product is “misbranded” if labeling is false or misleading
• Federal Trade Commission (FTC)
– Prohibits unfair and deceptive acts or practices
• National Advertising Division (NAD)
– Council of Better Business Bureaus
– Self-regulatory mechanism
• State Laws
ASTM Standards
• ASTM International
– Formerly American Society for Testing and Materials
• ASTM E-1958-06 Guide for Sensory Claim Substantiation
– Standard covers reasonable practices for designing and
implementing sensory tests that validate claims pertaining
only to the sensory or perceptual attributes, or both, of a
product.
FDA – Definitions of Cosmetics vs. Drugs
• Cosmetics:
"articles intended to be rubbed, poured, sprinkled, or sprayed on,
introduced into, or otherwise applied to the human body...for
cleansing, beautifying, promoting attractiveness, or altering the
appearance" [FD&C Act, sec. 201(i)]
• Drugs:
"(A) articles intended for use in the diagnosis, cure, mitigation,
treatment, or prevention of disease…and (B) 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)]
• Cosmeceuticals:
“A product can be a drug, a cosmetic, or a combination of both,
but the term "cosmeceutical" has no meaning under the law.”
How is intended use established?
• Claims stated on the product labeling, in advertising, on
the Internet, or in other promotional materials.
• Consumer perception, which may be established through
the product's reputation.
• Ingredients that may cause a product to be considered a
drug because they have a well known (to the public and
industry) therapeutic use.
http://www.cfsan.fda.gov/~dms/cos-218.html
FDA Warning Letter Excerpts
“The review of this labeling found the products being
offered are promoted for conditions that cause them to be
drugs under sections 201(g)(1)(B) and 201(g)(1)(C) of the
Federal Food, Drug, and Cosmetic Act (the Act) [21
U.S.C. 321(g)(1)(B) and 321(g)(1)(C)]. Claims in your
labeling, including your web sites, establish that these
products are drugs because they are intended for use in
the cure, mitigation, treatment, or prevention of disease
and are intended to affect the structure or function of the
body.”…
FDA Warning Letter Excerpts - Continued
Examples of some of the claims observed for these products include:
Claims on the boxes for each of your … products:
• "Reduces Redness"
• "Smoothes Scaly Skin"
Claims on the … Dramatic Relief for Oily and Acne Prone Skin box:
• "[I]ntended for individuals with chronic skin redness and flaking . . . associated
with dermatologic conditions like seborrheic dermatitis or rosacea ." …
• "Inflamed oily skin associated with troublesome dermatologic conditions. .
.Dramatic Relief. . .for Oily and Acne Prone Skin. . .clinically proven to reduce
redness, eliminate scaling, and help soft, smooth skin reappear."
Claims on the … Dramatic Relief for Normal To Dry Skin box:
• "[I]ntended for individuals with chronic skin redness accompanied by severely dry
skin, often associated with dermatologic inflammatory conditions like eczema or
rosacea." …
• "Inflamed, dry and scaly skin often associated with troublesome dermatologic
conditions. . . Dramatic Relief. . .for Normal to Dry Skin ... clinically proven to
reduce redness, eliminate scaling and itching, and help smooth, soft skin
reappear.“
NAD – Advertising Industry Self-Regulation
• Review national advertising for truthfulness and accuracy
– Routine monitoring of advertisements
– Mediate challenges between companies
• Review of challenges done within 60 business days
• Data are confidential, while advertiser and challenger
positions, and NAD decisions are available to the public
• Will refer to other government agencies (FTC) as
appropriate if advertisers do not cooperate
NAD Review - Example
Claims at issue:
• “Now it’s skincare that actually lifts wrinkles from the inside out.”
– NAD recommended that the company discontinue or modify the
claim … to reflect a reduction in the appearance of lines and
wrinkles, rather than the elimination of lines and wrinkles.
• “XXX with unique dermatological-nutrients refuels cells within skin’s
deepest surface layers: OMEGA 3 locks in moisture; VITAMIN A
visibly reduces wrinkles; RICE PROTEIN fortifies skin.”
– NAD determined that there is a reasonable basis to support the
“unique dermatological-nutrients” claim as it relates to OMEGA 3
and rice protein, but recommended the reference to Vitamin A be
modified to reflect that it helps reduce, rather than visibly reduces,
fine lines and wrinkles.
• “A clinical study proves: in 3 weeks wrinkles are visibly lifted and skin
is noticeably firmer.”
– NAD recommended that the claim … be modified to reflect the
wording of the company’s clinical study.
So, why do claims need substantiation?
• Comply with regulations
– Need to provide a reasonable basis for claims
• Consumer acceptance of the product!
– If product doesn’t meet expectations, there will be limited
success in the market place
Claim Substantiation Process
• Claims development process should begin early in the
product development process
• Product development driven by desired claims
• Review of claims by cross-functional team:
– Marketing
– R&D/Technical
– Regulatory Affairs
– Legal
– Product Safety
Claims Related Questions
• Is the product a cosmetic, drug, or medical device?
– Can changing the claim, change product
classification?
• Will claims be on package, on the internet, in print, or on
television?
• Do claims require testing to substantiate?
– What type of testing is required?
– Is there a standard or industry accepted method to
substantiate?
Categories of Claims
• Composition/Ingredient Claims
• Safety
• Efficacy/Performance
– Cosmetic
– Drug
Claims can be further classified as…
• Monadic
• Comparative
– Superiority
– Parity
Composition Claims
• “X contains Vitamin C, a potent anti-oxidant to help fight
visible signs of aging”
– How much vitamin C is present in formulation?
– Is it shown to be effective at that concentration?
– What form is it in?
– Is it effective in the formulation?
A note about claims relating to safety…
• FDA states:
– If the safety of a cosmetic is not adequately substantiated,
the product may be considered misbranded and may be
subject to regulatory action unless the label bears the
following statement: "Warning - The safety of this product
has not been determined." See 21 CFR 740.10.
Determining Cosmetic Product Safety
• Determination of product safety is the responsibility of the
manufacturer/marketing company
• Cosmetic Ingredient Review (CIR) panel
– Established in 1976 by the Cosmetic, Toiletry & Fragrance
Association (CTFA) with support FDA and the Consumer
Federation of America
– Thoroughly reviews and assesses the safety of ingredients
used in cosmetics in an open, unbiased, and expert
manner, and publishes the results in the open, peerreviewed scientific literature
Product Safety Testing
• Testing needs are determined by the company marketing the product
• May include:
– In vitro testing
– Cumulative Irritation testing
– Repeat Insult Patch Tests (RIPT)
• Sensitization
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–
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Ocular Irritation
Facial Sting
Phototoxicity
Photoallergy
Comedogenicity
Acnegenicity
Hypoallergenic
• No Federal standards or definitions of "hypoallergenic"
• Term is defined by the company making the claim
– Type of testing used to substantiate hypoallergenic varies
from company to company
Product Performance Claims
• It is the responsibility of the company marketing a
cosmetic product to substantiate performance claims.
• Types of testing and the degree of testing can vary widely
within the industry.
Creative cosmetic claims…
“Olay Regenerist regenerates skin's appearance without
such drastic measures as chemical peels, cosmetic surgery
or lasers. Clinical tests prove that amino-peptides help
regenerate damaged skin. Now Olay Regenerist uses this
technology to beautifully regenerate skin's appearance by
renewing its outer layer, revealing newer skin.
Regenerist Daily Regenerating Serum uses a concentrated
form of an exclusive amino-peptide complex and combines
it with Olay moisture to offer the maximum regeneration and
hydration within the Regenerist line. This formula leaves
your skin feeling velvety smooth and is designed for
everyday use.”
http://www.olay.com/boutique/regenerist/products/re1012
Cosmetic Claims
L’OREAL RevitaLift Double Lifting: The first double-action treatment
that instantly re-tightens skin and effectively fights wrinkles. The
double-pump system combines two exclusive formulas, an intense
re-tightening gel and an anti-wrinkle treatment, in just one application.
Benefit 1: The Intense Re-Tightening Gel, containing Pro-Tensium,
works to immediately form a resistant and flexible network that
instantly re-tightens skin. 75% of women reported skin lifted and
tightened immediately.*
*Effectiveness in a test of 52 women immediately after application.
Benefit 2: The Anti-Wrinkle Comfort Cream with Nanosomes of ProRetinol A penetrate the skin’s surface, effectively fighting wrinkles
and reducing the appearance of fine neck creases. 20% of women
tested had fewer surface wrinkles in one week.*
*Effectiveness in reduction of overall surface wrinkles in a test of 40
women.
http://www.lorealparisusa.com/frames.asp?0.5192384361169118#skincare/brand/revitalift.asp
OTC Drug Claims
• Limited by monographs
– Sunscreen claims
– Antimicrobial formulations
– Skin protectants
• Diaper rash cream
– Acne
– Skin bleaching
• Testing requirements addressed in monograph
OTC Example – Sunscreen
• Drug label claims:
– Helps prevent sunburn
– Broad spectrum sunscreen must provide at least low protection
against UVB and UVA
– Water Resistant/Very Water Resistant
• Retains SPF after [40 or 80] minutes of activity in the water [and/or
sweating or perspiring]
– SPF 50+
• Provides highest protection against sunburn and tanning
• For skin extremely sensitive to sunburn
• Testing is required to establish UVB SPF, UVA and water resistant
claims
– Test methodology found in monograph
OTC Example: Skin Protectant – Lip Protectant
• Drug label claims:
– Temporarily protects [and helps relieve] chapped or
cracked lips
– Helps protect lips from the drying effects of wind and cold
weather
• No testing requirements established by the monograph
• Additional cosmetic claims such as “moisturizing” allowed
outside of the Drug Facts box
Is testing needed to substantiate the claim?
• Puffery – typically cannot be tested or measured
• Technical Opinion – substantiation based on sound
technical judgment of expert in the field
• Substantiation testing – required, for example, when
claim speaks to effectiveness of a product or a benefit or
improvement in a skin attribute as a result of using the
product; in vivo or in vitro
Group Activity
• Identify the following types of claims in the magazine ads
provided:
– Composition claims
– Cosmetic claims
– Drug claims
• Which claims do you think need testing to substantiate?
Types of substantiation testing
• Laboratory Test (in vitro)
• Clinical Test (in vivo)
• Consumer Use Tests
Vendor Information, key questions to ask:
• What is the mechanism of action?
• How was it tested?
– Laboratory?
– Clinical?
– Use test?
• What concentrations of the ingredient were used?
• How many data points were captured?
• Were proper controls used?
• Are the methods clearly described?
• Is all of the data being presented?
• Is statistical significance demonstrated?
• Does the data support the vendor’s conclusions?
• How will this ingredient work in the final formulation?
What is a Clinical Study?
• Controlled investigation involving consenting human
volunteers
• Subjects recruited based on specific inclusion/exclusion
criteria – not necessarily “consumers”
• Follow Good Clinical Practices
• Designed to gain fundamental knowledge of a biological
condition or to evaluate test article safety, efficacy, or
specific product attributes
• Not typically preference, sensory, or consumer use tests
Categories of Skin Clinical Studies
• Fundamental skin research
• Evaluation of product performance or product
characteristics
• Claim substantiation
Study categories vs. Product Development timeline
Concept Development
Product Development
Product Launch
Fundamental Skin Studies
Post-Launch
Consumer
Feedback
Product Performance/Characteristics
Product
Improvements
Claim substantiation
Fundamental Skin Attributes
• Small number of subjects
• Often geared toward understanding differences between populations
or conditions
– Age: Infant, adult, elderly
– Race/Ethnicity: Caucasian, African-American, Latino, Asian
– Gender
– Condition: healthy intact skin vs. compromised skin
– Skin type: normal, oily, dry skin
Product Performance or Characteristics
• Small number of subjects
• Used to determine whether a product has a desired benefit
– Does the lotion moisturize for 24 hours?
– Is the antimicrobial lotion effective at killing bacteria?
• Compare multiple product prototypes
• Potential issues with a product
Claims Substantiation
• Larger numbers of subjects
• Designed to substantiate product claims
• Final product tested
• Target population
• May utilize normal usage instructions
Factors to Consider when Developing a Protocol
• Population
• Number of subjects
• Methodology
• Study length
• Product availability
• Product Classification
– Cosmetic, drug, or medical device
• Institutional Review Board (IRB) approval
• ASTM Guidelines (if using as an Ad Claim)
Where should the study be placed?
• Several specialized test facilities throughout US
• Capabilities – strengths/weakness
• Geographic location
– Climate
• Population base
• Flexibility of timing
• Cost
Methodology
• Instrumental Evaluation
• Expert Grade
• Subject Self-Assessment
Instrumental Measurements
• Advantages
– Objective measurements
– May provide increased sensitivity
• Disadvantages
– Effect may be more complex than one instrument can
measure
– Differences detected by instrumentation may not be
meaningful to consumers
Examples of Instrumental Measurements
• Moisturization → Conductance/Impedance
• Skin barrier function → TEWL
• Skin texture → Topography
• Skin elasticity → Elastometer
• Skin thickness → Ultrasound
• Skin surface characteristics → Microscopy
• Temperature → Infrared Thermography
• pH → Skin pH probe
• Color → Chromameter
• Blood flow→ Laser Doppler
• Sebum (oiliness) → Sebumeter
Moisturization
• Measurement based on the premise that electrical
properties of the skin change with hydration
• Instruments that measure skin conductance, impedance,
and capacitance used to measure skin hydration
– Skicon (IBS Co. Ltd., Japan) – conductance
– Dermalab (Cortex, Denmark) - conductance
– Corneometer (Courage + Khazaka Electronic GmbH,
Germany) – capacitance
– Nova™ Dermal Phase Meter (DPM) (Nova Technologies,
US) – impedance
Skin Barrier
• Transepidermal Water Loss (TEWL) is used to measure
vapor loss from the skin
– Tewameter (Courage + Khazaka Electronic GmbH,
Germany)
– Dermalab (Cortex, Denmark)
– Servo Med Evaporimeter (Servo Med, Sweeden)
Skin Texture
• Topography can be measured through profilometry
measurements
– Silicone Replicas
• Skin-Visiometer® SV 600 (Courage + Khazaka Electronic
GmbH, Germany)
– Laser Profilometry
Fine Lines/Wrinkles
• Can be done in similar fashion to skin texture
measurements
– Silicone Replicas
• Digital image assessments
– PRIMOS (GFMesstechnik GmbH , Germany) – 3D
imaging
Photography Systems
• Canfield VISIA
– Facial photography
• Front and side images
– Standard lighting
• Standard flash
• Parallel Polarized
– Accentuate surface characteristics
• Cross Polarized
– Accentuates sub-surface characteristics
• UV
– Sun damage
– Acne
Skin Elasticity
• A number of techniques can be used to measure the
mechanical properties of the skin
– Dermal Torque Meter (Diastron, UK)
• Torsion
– Dermlab Elasticity Module (Cortex, Denmark)
• Suction
– Ballistometer (Diastron, UK)
• Indentation
Skin Thickness
• Can be measured using ultrasound techniques
Dorsal Forearm
25 year old
51 year old
20 MHz Sharp Focus Transducer
Temperature
• Infrared Thermography
– Used to measure skin surface temperature
• Thermocouples
– Can measure heat between surfaces
Blood Flow
• Laser Doppler imaging can be used to assess blood flow
which can be associated with irritation or heat
Lower back before and after heating pad use
Color
• Various imaging techniques can be used for assessing
redness, tanning, and overall skin color
– Chroma Meter (Konica Minolta, Japan)
• Uses L*a*b* color space system
– DSM Color Meter (Cortex, Denmark)
• Measuring erythema and melanin
Expert Grade
• Advantages
– Can assess multiple parameters at once
– Assess features for which there is no instrumental measurement
available
– Provide more consistency than subject self-assessment
• Disadvantages
– Subjective measurements
– Differences may not be perceived by consumers
– Should be trained and able to demonstrate repeatable,
consistent responses
– More expensive
– Advantageous to have more than one, but not always practical
Examples of Traits Assessed by Expert Grader
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•
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•
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•
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Skin Dryness/Moisturization
Irritation
Fine lines
Dark circles (under eye)
Puffiness (under eye)
Texture/Smoothness
Color
Radiance
Clarity
Youthfulness
Subject Self-Assessment
• Advantages
– Assessments most similar to consumer perception
– Most meaningful to consumer
• Disadvantages
– Subjective measurements
– Larger sample sizes to differentiate (noisier data)
– Subjects will sometimes perceive differences that are
not detected by other means
Subject Self-Assessment
• Can evaluate same attributes as expert grade
• Mirror evaluations
– Less expensive
– Perception changes over time
• Photography
– Allows subjects to compare baseline photos to posttreatment photos
• Both types of assessments require controlled and
consistent lighting
Study Design
• Objective
• Inclusion/Exclusion Criteria
• Methods
– Pretreatment Phase
– Treatment Phase
• Data Analysis
Forearm Moisturization Study - Example
• 30 subjects
• Six test sites (including one control site)
• Acclimation to controlled temperature & humidity environment
• Baseline conductance measurements taken
• Apply controlled amount of formulation to each test site
• Take additional conductance measurements: 30 minutes to 24
hours after application
• Compare pre- and post-application measurements
• Compare test and untreated control sites
Fine Line/Wrinkle Study – Example
• 30 subjects
• Periorbital and/or perioral wrinkles present
• Baseline instrumental, expert grade, and subject selfassessment (photography)
• Subjects use product twice daily for up to 12 weeks
• Fine line assessments repeated periodically
• Compare to baseline measurements
Questions?
References
• Food & Drug Administration (FDA)
http://www.fda.gov/
– Over the Counter (OTC) Drug
http://www.fda.gov/cder/offices/otc/default.htm
• National Advertising Division (NAD)
http://www.nadreview.org/
• Federal Trade Commission
http://www.ftc.gov/
• Cosmetic, Toiletry, and Fragrance Association (CTFA)
http://www.ctfa.org/
• Cosmetic Ingredient Review
http://www.cir-safety.org/
• American Society for Testing and Materials (ASTM)
http://www.astm.org/
• Bioengineering of the Skin: Methods and Instrumentation. 1995. Eds. E. Berardesca,
P. Elsner, K. P. Wilhelm, H. I. Maibach
• Skin Moisturization. 2002. Eds. J. J. Leyden, A. V. Rawlings