1 Testing For Safety & Efficacy Alain Khaiat PhD Vice President R&D Johnson and Johnson Asia...

1

Testing

For

Safety & Efficacy

Alain Khaiat PhD

Vice President R&D

Johnson and Johnson Asia Pacific

2

• Cumulative Irritation:– To determine the irritation potential of topical product

left on skin. • Sensitization (RIPT):

– To determine the potential of a product to cause allergic contact response.

• Photo-toxicity: – To assess the potential of ingredients to cause localized

irritant reactions when exposed to sunlight

• Photosensitization:– To determine the potential of a product to cause allergic

contact response when exposed to sunlight.

Testing for SafetyTesting for Safety

3

Cumulative Irritation• 25 volunteers• Occlusive patch applied for 48 to 72 hours

RIPT - Predictive testing for skin sensitizers.• 100 - 200 volunteers• 10, 48 hr Patches - 3 weeks• Rest period - 2 weeks• Challenge 48hr at new skin site.

Safety TestingSafety Testing

4

Phototoxicity– 20 volunteers– 1 dose– 0, 24, hr exposure & patches– Read @ 48, 72 hr

Photoallergy– 25 volunteers, fair skinned– Induction phase – twice/week for 3 weeks. Reading &

irradiated 24 hrs after patching– Rest period – 2 weeks– Challenge phase – Patch at new skin site. Read @ 24,

48, 72 hrs

Safety TestingSafety Testing

EYE MILDNESSEYE MILDNESS

6

Ocular SafetyOcular Safety

Suggested Test Criteria

Transepithelial Permeability (TEP)

MDCK CellsCorneal Epithelium

•MDCK cells grown to confluence •Tight junctions b/w cells form an impermeable barrier•Dye marker will not cross undamaged cell layer

In-vitro Screening: EC50 TEP Rating

2.20 or higher PASS1.8 - 2.19 Borderline1.79 or lower FAIL

EC50 = test pdt concn where 50% of the max amount of dyeto leak through the barrier into the lower well.

7

Required Tests Criteria

In-Vivo Test:

Human Ocular Irritation Test Stinging at time of installationWhich is not statistically higher than sterile water control

• Panel of 10 subjects• Supervised by an opthalmologist • Subject focus on any minor discomfort in their eyes after application of warmed test products.• Measures sting, lacrimation, irritation•One eye receives 10% conc of test substance and the other eye receives distilled water

When 5 subjects (or more) experience larger responses on test product than to water, the test product will generally failto be “non – irritating” to the eye

Ocular SafetyOcular Safety

MOISTURIZATIONMOISTURIZATION

9

MoisturizationMoisturization

Test Subjects:Test Subjects:• Female adults, usually 20 to 55 yrs oldFemale adults, usually 20 to 55 yrs old• In good health, no allergy to cosmeticsIn good health, no allergy to cosmetics• Normal to Dry skinNormal to Dry skin

10


Test Design:Test Design:• Base size of 10 to 20Base size of 10 to 20• RandomizedRandomized• Control – untreated skin and/or benchmarkControl – untreated skin and/or benchmark

11


Test Site:Test Site:• 4cm x 8cm rectangle on volar forearm4cm x 8cm rectangle on volar forearm• Usually 2 test sites per armUsually 2 test sites per arm

Product Usage:Product Usage:• 0.1mL per test site0.1mL per test site

12


Before the test:Before the test:• No leave-on products 24 hours beforeNo leave-on products 24 hours before• No caffeinated drinks 1 hour before No caffeinated drinks 1 hour before • 30-minute acclimatization to room conditions30-minute acclimatization to room conditions

13


Instrumental Evaluations:Instrumental Evaluations:• Baseline, 1, 4, 8, (12), (24) hoursBaseline, 1, 4, 8, (12), (24) hours• SkiconSkicon®® – Conductance – Conductance• TewameterTewameter®® – TEWL – TEWL • Visioscan® ® – Surface roughness– Surface roughness

14


Success Criteria:Success Criteria:• Increase in conductance vs. baselineIncrease in conductance vs. baseline• Higher increase vs. control/benchmarkHigher increase vs. control/benchmark

• Reduction in TEWL vs. baselineReduction in TEWL vs. baseline• Higher reduction vs. control/benchmarkHigher reduction vs. control/benchmark

15


Other Considerations:Other Considerations:• For wash-off products, need to do longer term For wash-off products, need to do longer term

studies e.g. 2 weeksstudies e.g. 2 weeks

16

Claim:Claim: Moisturizes, hydrates Moisturizes, hydrates

Suggested Tests/Data• Instrumental

• Skicon (based on conductance)

• Corneometer (based on capacitance)

• TEWAmeter

Criteria• Increase in parameter

versus baseline, untreated skin or benchmark (0, 2, 4, 6, 8, 24 hours, weeks)

Criteria• Decrease in trans-

epidermal water loss versus baseline, untreated skin or benchmark (0, 2, 4, 6, 8, 24 hours)

17

Claim:Claim: Prevents symptoms of Prevents symptoms of dry skin dry skin

Suggested Tests/Data• Derm Assessment

• Dryness• Scaling• Erythema

• Instrumental• Skicon/Corneometer• TEWAmeter• Erythema Index• Digital Photography

• Self-Assessment• Irritation

Criteria

• Improvement in grading vs. baseline, untreated skin or benchmark

• Improvement in parameter vs. baseline, untreated skin or benchmark

• Improvement in grading vs. baseline, untreated skin or benchmark

Claims related to products which treat Claims related to products which treat or prevent Acne and Pimplesor prevent Acne and Pimples

19

Reaches deep down into pores

Contains a blackhead fighting medicine

Prevents future blackheads

Oil Free

Won’t overdry your skin

Removes oil, dirt and make-up

Non-comedogenic

Long lasting oil control

20

AcneAcne

Test Subjects:Test Subjects:• Female adults, usually 20-35 yrs oldFemale adults, usually 20-35 yrs old• In good health, no allergy to cosmeticsIn good health, no allergy to cosmetics• Mild to Moderate Acne Mild to Moderate Acne

21

AcneAcne

Test Design:Test Design:• Base size of 30 to 50Base size of 30 to 50• Double-Blind, RandomizedDouble-Blind, Randomized• Control – vehicle and/or benchmarkControl – vehicle and/or benchmark

22

AcneAcne

Test Site:Test Site:• Whole face Whole face

Product Usage:Product Usage:• Normal or habitual useNormal or habitual use• Usually 2x dailyUsually 2x daily

23

AcneAcne

During the study:During the study:• Use of skin care products with active Use of skin care products with active

ingredients NOT allowedingredients NOT allowed

24

AcneAcne

Clinical Evaluations:Clinical Evaluations:• Baseline, 1, 2, 4, 8 weeks Baseline, 1, 2, 4, 8 weeks • Overall Acne Severity (Cook’s Grading Scale)Overall Acne Severity (Cook’s Grading Scale)• Lesion Count – papules, pustules, open & Lesion Count – papules, pustules, open &

closed comedonesclosed comedones

25

AcneAcne

Instrumental Evaluations:Instrumental Evaluations:• SkinskanSkinskan®® – inflammation – inflammation• DRS – erythemaDRS – erythema• PRIMOSPRIMOS®® – size & elevation – size & elevation• Photography – overall improvement Photography – overall improvement

26

AcneAcne

Success Criteria:Success Criteria:• Improvement vs. baselineImprovement vs. baseline• Better improvement vs. vehicleBetter improvement vs. vehicle• Better improvement vs. benchmark Better improvement vs. benchmark

Other Considerations:Other Considerations:• Inclusion of safety assessment e.g. erythema, Inclusion of safety assessment e.g. erythema,

edema, dryness, scalingedema, dryness, scaling

27

Claim:Claim: Helps treat and prevent Helps treat and prevent pimples and blackheadspimples and blackheads

Suggested Tests/Data• The product contains a

keratolytic agent

• Self assessment (150-based consumer research)

• Instrumental Measures and

Derm assessment.

Criteria• E.g. Salicylic Acid 0.5-2.0%

Statistically significant results vs baseline/control/ benchmark

• Digital photography. Numerical count of lesions, Dermatological Grading (versus visual standards).

28

Example of Dermatologist Grading Scale:Modified Cook’s Grading scale

29

Claim:Claim: Keeps pores unclogged Keeps pores unclogged

Suggested Tests/Data• The product contains a

keratolytic agent, exfoliant or absorbent.


Criteria• E.g. Salicylic Acid, AHA,

Benzoyl Peroxide,

Polyethylene, Silica, Kaolin.

• Statistically significant results vs baseline/control/ benchmark

30

Claim:Claim: Oil-Free Oil-Free

Suggested Tests/Data• The product does not

contain any ingredient that would be considered an oil.

Criteria• The CTFA/INCI

ingredient listing for each ingredient does not contain the word “oil”.

31

Claim:Claim: Reduces skin rednessReduces skin redness

Required Tests/Data• Derm assessment

and Instrumentation

Criteria• Grading on Erythema

Scale (0-none to 4-severe)

• Chromameter a-value,

Mexameter Erythema Index, Digital Photography (before and after)

32

Claim:Claim: Anti-bacterialAnti-bacterial

Suggested Tests/Data• The product contains

ingredients with proven anti-bacterial activity against p.acnes (propionibacterium acnes)

Criteria• Effective dosage levels of

anti-bacterial agent, e.g. Salicylic Acid 0.5 -2.0%, Triclosan 0.1%.

• A 10% solution of the product should be able to inhibit p. acnes.

33

Oil ControlOil Control

Test Subjects:Test Subjects:• Female teens, usually 13-19 yrs oldFemale teens, usually 13-19 yrs old• In good health, no allergy to cosmeticsIn good health, no allergy to cosmetics• Normal to Oily skin Normal to Oily skin

34



35


Test Site:Test Site:• Forehead and/or naso-labial fold Forehead and/or naso-labial fold


36


Before the study:Before the study:• No leave-on products 24 hours beforeNo leave-on products 24 hours before• Face must be cleansed 4 hours before Face must be cleansed 4 hours before • No caffeinated drinks 1 hour beforeNo caffeinated drinks 1 hour before • 30-minute acclimatization to room conditions30-minute acclimatization to room conditions

37


Instrumental Evaluations:Instrumental Evaluations:• Baseline, 1, 2, 4, 8 weeks Baseline, 1, 2, 4, 8 weeks • SebumeterSebumeter®® – sebum level ( – sebum level (g/cmg/cm22))• SebufixSebufix® ® – pixels of sebum – pixels of sebum • Photography – shine/glare on the face Photography – shine/glare on the face

38


Success Criteria:Success Criteria:• Reduction in sebum vs. baselineReduction in sebum vs. baseline• Higher reduction vs. vehicleHigher reduction vs. vehicle• Higher reduction vs. benchmarkHigher reduction vs. benchmark

39




40

Claim:Claim: Oil ControlOil Control

Suggested Tests/Data• Sebum Reduction

• Sebutape™ • Sebumeter


• Lipase Analysis via HPLC

Criteria• Chromatographic

analysis of sebum (baseline, and at 2, 4, 6 and 8hrs).

• Skin sebum levels

• Statistically significant data vs baseline/control/ benchmark

• A statistical significant reduction in triglycerides and fatty acids.

41

Claim:Claim: Deep cleanses to Deep cleanses to remove oil and impuritiesremove oil and impurities

SuggestedTests/Data• Self assessment

(150-based consumer research)

• Sebutape, Sebumeter

Criteria• Statistically significant

results vs baseline/control/ benchmark

• The % change in sebum after washing with water versus washing with test product.

Claims related to Sunscreen ProductsClaims related to Sunscreen Products

43

Protects against skin aging UVA rays

Protects against skin burning UVB rays

Fights damaging free radicals

Oil-Free

Non-comedogenic (won’t clog your pores)

Recommended by dermatologists

SPF 45

Waterproof

Sweatproof

44

Claim:Claim: Sun Protection Factor Sun Protection Factor SPF 15, 30, 45SPF 15, 30, 45

Required Tests/Data• US FDA Sun Protection

Factor Method

(Australia uses their own method.)

Criteria• 20 person test. Males

and Females. Fair skinned – Type I, II, and III.

45

Claims:Claims: Broad Spectrum Protection, Broad Spectrum Protection, Protects against skin-aging UVA rays,Protects against skin-aging UVA rays,

Protects against skin-burning UVB rays Protects against skin-burning UVB rays.

Required Tests/Data• Spectrophotometric

Analysis

(300-400nm)

Criteria• The product must not

transmit more than 10% UV radiation at any wavelength between 320-360nm.

46

Claim:Claim: Waterproof for “x” hours Waterproof for “x” hours

Required Tests/Data• US FDA Immersion Test

Criteria• SPF rating after the

prescribed immersion time.

47

Claims:Claims: Protects against / Protects against / fights damaging free radicalsfights damaging free radicals

Suggested Tests/Data• This type of claim relates

to specific ingredients with anti-oxidant functions.

• In-vitro antioxidant, anti-ozone, anti-pollution activity

Criteria• An effective

concentration of Vitamin E, C, AA2G, BHT, Lycopene etc.

• No changes in skin markers with product when exposed to pollutants

FAIRNESSFAIRNESS

49

LighteningLightening

Test Subjects:Test Subjects:• Female adults, usually 25-55 yrs oldFemale adults, usually 25-55 yrs old• In good health, no allergy to cosmeticsIn good health, no allergy to cosmetics• Preferably with slight to moderate dark skin Preferably with slight to moderate dark skin

tone tone

50



51




52




53


Clinical Evaluations:Clinical Evaluations:• Baseline, 4, 8, 12 weeks Baseline, 4, 8, 12 weeks • Overall FairnessOverall Fairness• Overall Evenness Overall Evenness • Spot LighteningSpot Lightening• SallownessSallowness

54


Instrumental Evaluations:Instrumental Evaluations:• ChromameterChromameter®® – L* (white), a* (red), b* – L* (white), a* (red), b*

(yellow)(yellow)• MexameterMexameter®® – melanin, erythema – melanin, erythema• DRS – melanin, hemoglobinDRS – melanin, hemoglobin• Photography – overall improvementPhotography – overall improvement

55


Success Criteria:Success Criteria:• Improvement vs. baselineImprovement vs. baseline• Better improvement vs. vehicleBetter improvement vs. vehicle• Better improvement vs. benchmarkBetter improvement vs. benchmark



56

Claim:Claim: Lightens skinLightens skin

Suggested Tests/Data• Derm assessment

• Overall Fairness

Criteria• Change in grading using a

standard scale versus baseline, vehicle or untreated skin

• 0 (lightest) to 9 (darkest) scale• Scale developed per subject

57


• Chromameter® L-value

• Mexameter ® Melanin Index

• Diffuse Reflectance Spectroscopy

• Digital Photography Pixel Luminosity Value

• Self assessment (150-base consumer research)

Criteria• Change in parameter versus

baseline, vehicle or untreated skin


Claim:Claim: Lightens skinLightens skin

58


• Age Spots / Sun spots• Mottled Hyperpigmentation

• Instrumental• Mexameter ® Melanin Index




standard scale versus baseline, vehicle, untreated spot or adjacent skin

• Change in parameter versus baseline, vehicle, untreated spot or adjacent skin

Claim:Claim: Reduces dark spots and Reduces dark spots and other hyperpigmentationother hyperpigmentation

59

Suggested Tests/Data• Solar UV Simulation


Criteria• Reduction in color post-

treatment of UV-irradiated skin


Claim:Claim: Reduces dark spots and Reduces dark spots and other hyperpigmentationother hyperpigmentation

60


• Overall Evenness

• Instrumental• Chromameter ® L-value

• Mexameter ® Melanin Index





• Lower std. dev. in parameter versus baseline, vehicle or untreated skin

Claim:Claim: Evens skin tone Evens skin tone

61

Suggested Tests/Data• Self assessment

(150-base consumer research)

Criteria• Statistically significant results

vs baseline/control/ benchmark

Claim:Claim: Evens skin tone Evens skin tone

62


• Overall Fairness

• Instrumental• Chromameter ® L-value• Mexameter ® Melanin Index • Diffuse Reflectance

Spectroscopy • Digital Photography Pixel

Luminosity Value

• Solar UV Simulation


Criteria• No change in grading using a

standard scale versus baseline or untreated skin even with sun exposure

• No change in parameter versus baseline or untreated skin even with sun exposure

• No change in color of pre-treated skin when irradiated with UV


Claim:Claim: Prevents darkening Prevents darkening

63


• Sallowness

• Instrumental• Chromameter ® b-value

• Digital Photography

• Self assessment




• Change in parameter versus baseline, vehicle or untreated skin


Claim:Claim: Reduces sallowness Reduces sallowness

64


• Overall Radiance• Overall Clarity

• Self assessment





Claim:Claim: Makes skin more radiant Makes skin more radiantBoosts skin clarityBoosts skin clarity

65

Required Tests/Data• Instrumental

• Video Camera (dead skin cells)

• Optical 3D Measurement (roughness)


• Fluorescence Technique



Claim:Claim: Makes skin more radiant Makes skin more radiantBoosts skin clarityBoosts skin clarity

66

Required Tests/Data

• In-vitro • Reaction of melanoma cells

with the specific ingredient• Reaction of tyrosinase with

the specific ingredient

• Skin Penetration Study• Cadaver Skin

Criteria• Reduction in melanoma cells

or tyrosinase

• Ingredient still to be detected by HPLC below epidermis level

Claim:Claim: Proven whitening Proven whitening ingredient, deposits to the skiningredient, deposits to the skin

ADVANCED SKIN CARE CLAIMSADVANCED SKIN CARE CLAIMS

68

• Derm and consumer self-assessment are still used to support these claims. Methodology and criteria are basically the same (e.g., change versus baseline, vehicle or untreated skin).

• However, advanced claims are mostly generated due to advancement in instrumental measurements.

Advanced Skin Care ClaimsAdvanced Skin Care Claims

69


• Viscoelastic Measurements (Cutometer ®)

• Collagen/Elastin Orientation (Reviscometer ®)

• Optical 3D Measurement

• Fluorescence / Microscopy



Claim:Claim: Firms skin Firms skin

70

Anti-AgingAnti-Aging

Test Subjects:Test Subjects:• Female adults, usually 35-55 yrs oldFemale adults, usually 35-55 yrs old• In good health, no allergy to cosmeticsIn good health, no allergy to cosmetics• Visible wrinkles, hyperpigmentation Visible wrinkles, hyperpigmentation

71



72




73




74


Clinical Evaluations:Clinical Evaluations:• Baseline, 4, 8, 12 weeks Baseline, 4, 8, 12 weeks • WrinklesWrinkles• LaxityLaxity• HyperpigmentationHyperpigmentation• Sallowness Sallowness

75


Instrumental Evaluations:Instrumental Evaluations:• CutometerCutometer®® - elasticity - elasticity• PRIMOSPRIMOS®® - wrinkles - wrinkles• Photography – overall improvement Photography – overall improvement

76


Success Criteria:Success Criteria:• Improvement vs. baselineImprovement vs. baseline• Better improvement vs. vehicleBetter improvement vs. vehicle• Better improvement vs. benchmark Better improvement vs. benchmark



77


• Profilometry (Replicas)

• Optical 3D Measurement



Claim:Claim: Reduces wrinkles, pore Reduces wrinkles, pore size or scar depthsize or scar depth

78


• Thermal Imaging

• Laser Doppler Blood Perfusion



Claim:Claim: Warms, soothes, calms, Warms, soothes, calms, enhances blood circulationenhances blood circulation

1 Testing For Safety & Efficacy Alain Khaiat PhD Vice President R&D Johnson and Johnson Asia...

Documents

Transcript of 1 Testing For Safety & Efficacy Alain Khaiat PhD Vice President R&D Johnson and Johnson Asia...