Skin Care Products: Claim Substantiation

1
Skin Care ProductsClaim Substantiation
Clinical Testing

• Barbara Dvoracek
• Senior Research Scientist
• Kimberly-Clark Corporation

Benedictine University Cosmetic
Chemistry November 13, 2007
2
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

3
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

4
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. 

5
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" FDC Act, sec.
  201(i)
• Drugs
• "(A) articles intended for use in the
  diagnosis, cure, mitigation, treatment, or
  prevention of diseaseand (B) articles (other
  than food) intended to affect the structure or
  any function of the body of man or other animals"
  FDC 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.

6
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

7
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.

8
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
• "Intended 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
• "Intended 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.

9
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

10
NAD Review - Example

• Claims at issue
• Now its 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 skins 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 companys clinical
  study.

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So, why do claims need substantiation?

• Comply with regulations
• Need to provide a reasonable basis for claims
• Consumer acceptance of the product!
• If product doesnt meet expectations, there will
  be limited success in the market place

12
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
• RD/Technical
• Regulatory Affairs
• Legal
• Product Safety

13
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?

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Categories of Claims

• Composition/Ingredient Claims
• Safety
• Efficacy/Performance
• Cosmetic
• Drug

15
Claims can be further classified as

• Monadic
• Comparative
• Superiority
• Parity

16
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?

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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.

18
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, peer-reviewed scientific
  literature

19
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
• Ocular Irritation
• Facial Sting
• Phototoxicity
• Photoallergy
• Comedogenicity
• Acnegenicity

20
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

21
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.

22
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/r
egenerist/products/re1012
23
Cosmetic Claims

• LOREAL 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 Pro-Retinol A penetrate the skins
  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?0.5192384
361169118skincare/brand/revitalift.asp
24
OTC Drug Claims

• Limited by monographs
• Sunscreen claims
• Antimicrobial formulations
• Skin protectants
• Diaper rash cream
• Acne
• Skin bleaching
• Testing requirements addressed in monograph

25
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

26
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

27
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

28
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?

29
Types of substantiation testing

• Laboratory Test (in vitro)
• Clinical Test (in vivo)
• Consumer Use Tests

30
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 vendors conclusions?
• How will this ingredient work in the final
  formulation?

31
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

32
Categories of Skin Clinical Studies

• Fundamental skin research
• Evaluation of product performance or product
  characteristics
• Claim substantiation

33
Study categories vs. Product Development timeline
Concept Development Product
Development Product Launch Post-Launch
Fundamental Skin Studies
Consumer Feedback
Product Performance/Characteristics
Product Improvements
Claim substantiation
34
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

35
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

36
Claims Substantiation

• Larger numbers of subjects
• Designed to substantiate product claims
• Final product tested
• Target population
• May utilize normal usage instructions

37
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)

38
Where should the study be placed?

• Several specialized test facilities throughout US
• Capabilities strengths/weakness
• Geographic location
• Climate
• Population base
• Flexibility of timing
• Cost

39
Methodology

• Instrumental Evaluation
• Expert Grade
• Subject Self-Assessment

40
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

41
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

42
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

43
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)

44
Skin Texture

• Topography can be measured through profilometry
  measurements
• Silicone Replicas
• Skin-Visiometer SV 600 (Courage Khazaka
  Electronic GmbH, Germany)
• Laser Profilometry

45
Fine Lines/Wrinkles

• Can be done in similar fashion to skin texture
  measurements
• Silicone Replicas
• Digital image assessments
• PRIMOS (GFMesstechnik GmbH , Germany) 3D
  imaging

46
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

47
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

48
Skin Thickness

• Can be measured using ultrasound techniques

Dorsal Forearm 25 year old
51 year old 20 MHz Sharp Focus Transducer
49
Temperature

• Infrared Thermography
• Used to measure skin surface temperature
• Thermocouples
• Can measure heat between surfaces

50
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
51
Color

• Various imaging techniques can be used for
  assessing redness, tanning, and overall skin
  color
• Chroma Meter (Konica Minolta, Japan)
• Uses Lab color space system
• DSM Color Meter (Cortex, Denmark)
• Measuring erythema and melanin

52
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

53
Examples of Traits Assessed by Expert Grader

• Skin Dryness/Moisturization
• Irritation
• Fine lines
• Dark circles (under eye)
• Puffiness (under eye)
• Texture/Smoothness
• Color
• Radiance
• Clarity
• Youthfulness

54
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

55
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
  post-treatment photos
• Both types of assessments require controlled and
  consistent lighting

56
Study Design

• Objective
• Inclusion/Exclusion Criteria
• Methods
• Pretreatment Phase
• Treatment Phase
• Data Analysis

57
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

58
Fine Line/Wrinkle Study Example

• 30 subjects
• Periorbital and/or perioral wrinkles present
• Baseline instrumental, expert grade, and subject
  self-assessment (photography)
• Subjects use product twice daily for up to 12
  weeks
• Fine line assessments repeated periodically
• Compare to baseline measurements

59
Questions?
60
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