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Safety & EfficacySafety & Efficacyof Cosmeticsof Cosmetics
New rules of theNew rules of theEuropean CommissionEuropean Commission
Nicola LionettiNicola LionettiL.L. Rigano Rigano IndustrialIndustrial ConsultingConsulting & & ResearchResearchISPE ISPE –– InstituteInstitute of of SkinSkin ProductProduct Evaluation
ISPE srlEvaluation
Regulation (EC) 1223/2009 of the Regulation (EC) 1223/2009 of the European ParliamentEuropean Parliamentand of the Counciland of the Council
of the 30of the 30 November 2009November 2009on cosmetic productson cosmetic products
(recast)(recast)
http://http://eureur‐‐lex.europa.eulex.europa.eu//LexUriServLexUriServ//LexUriServ.doLexUriServ.do??
uri=OJuri=OJ:L:2009:342:0059:0209:en:PDF:L:2009:342:0059:0209:en:PDF
Entry into force & date of applicationEntry into force & date of application
11 January 2010 (20 d publication Official 11 January 2010 (20 d publication Official
Journal)Journal)
Only for CMR Only for CMR ⇒⇒ 1 December 20101 December 2010
New Notification New Notification ⇒⇒ 11 January 201211 January 2012
NanomaterialNanomaterial ⇒⇒ 11 January 201211 January 2012
1111 July 2013July 2013
RegulationRegulation 1223/20091223/2009
Mainly a RECASTMainly a RECAST
Clarification/Explication on:Clarification/Explication on:
Responsible Person (RP)Responsible Person (RP)
Good Manufacturing Practice (GMP)Good Manufacturing Practice (GMP)
Supply Chain & Market SurveillanceSupply Chain & Market Surveillance
Safety of the CosmeticsSafety of the Cosmetics
PProof of the effect claimedroof of the effect claimed
Regulation 1223/2009Regulation 1223/2009New rules on:New rules on:
Cosmetic Notification (CPNP)Cosmetic Notification (CPNP)
NanomaterialsNanomaterials (def. & Notification)(def. & Notification)
CMRCMR
Label IndicationsLabel Indications
Underline thePIF address
Titanium Dioxide (nano)
RegulationRegulation 1223/20091223/2009ImprovesImproves
FREE CIRCULATIONFREE CIRCULATION
SAFETYSAFETY
CLAIMCLAIM
of COSMETICSof COSMETICS
Safety AssessmentSafety Assessment
Little DigressionLittle Digression
Clarification/Explication ?Clarification/Explication ?Safety of the CosmeticsSafety of the Cosmetics
Article 7a, paragraph d (Directive 76/768)Article 7a, paragraph d (Directive 76/768)Assessment of the safety for human health of the finished producAssessment of the safety for human health of the finished product. To that t. To that end the manufacturer shall take into consideration the general tend the manufacturer shall take into consideration the general toxicological oxicological profile of the ingredients, their chemical structure and their lprofile of the ingredients, their chemical structure and their level of exposure. evel of exposure. It shall take particular account of the specific exposure characIt shall take particular account of the specific exposure characteristics of the teristics of the areas on which the product will be applied or of the population areas on which the product will be applied or of the population for which it is for which it is intended. There shall be inter intended. There shall be inter aliaalia a specific assessment for cosmetic products a specific assessment for cosmetic products intended for use on children under the age of three and for cosmintended for use on children under the age of three and for cosmetic products etic products intended exclusively for use in external intimate hygieneintended exclusively for use in external intimate hygiene
SCCNFP/0690/03, Final : Notes of Guidance for the testing of cosSCCNFP/0690/03, Final : Notes of Guidance for the testing of cosmetic metic ingredients and their safety evaluation, 5th revision, adopted bingredients and their safety evaluation, 5th revision, adopted by the SCCNFP y the SCCNFP during the 25th plenary meeting of 20 October 2003during the 25th plenary meeting of 20 October 2003
Safety ReportSafety ReportArt. 11 Art. 11 –– Product Information File shall contain:Product Information File shall contain:
‐‐ …………....‐‐ cosmetic product safety report (CSR)cosmetic product safety report (CSR)
Art. 10 Art. 10 –– CSR:CSR:‐‐ guaranteed by RPguaranteed by RP‐‐ kept up to datekept up to date‐‐ carried out by qualified personcarried out by qualified person(pharmacy, toxicology, medicine or a similar discipline, or a (pharmacy, toxicology, medicine or a similar discipline, or a course course recognisedrecognised as equivalent by Member State)as equivalent by Member State)
Safety ReportSafety ReportArt. 10 Art. 10 –– CSR:CSR:
‐‐ The Commission, in close cooperation with all The Commission, in close cooperation with all stakeholders, shall adopt appropriate stakeholders, shall adopt appropriate
guidelinesguidelines to enable undertakings, in to enable undertakings, in particular small and mediumparticular small and medium‐‐sized enterprises, sized enterprises, to comply with the requirements laid down in to comply with the requirements laid down in
AnnexAnnex II..
Annex IAnnex ICOSMETIC PRODUCT SAFETY REPORT
The cosmetic product safety report shall, as a minimum, contain the following
PART A – Cosmetic product safety information
PART B – Cosmetic product safety assessment
RISK ASSESSMENT
Annex IAnnex IPART A – Cosmetic product safety information
1. Quantitative & qualitative composition cosmetic product
2. Physical/chemical characteristics & stability
3. Microbiological quality
4. Impurities, traces, information on packaging material
5. Normal & reasonably foreseeable use
Annex IAnnex IPART A – Cosmetic product safety information
6. Exposure to the cosmetic product
7. Exposure to the substances
8. Toxicological profile of the substances
9. Undesirable effects & serious undesirable effects
10. Information on the cosmetic product
Annex IAnnex IPART B – Cosmetic product safety assessment
1. Assessment conclusion
2. Labelled warnings and instructions of use
3. Reasoning
4. Assessor’s credentials and approval of part B
Annex IAnnex IPART A – Cosmetic product safety information
1. Quantitative & qualitative composition cosmetic product
2. Physical/chemical characteristics & stability
3. Microbiological quality
4. Impurities, traces, information on packaging material
5. Normal & reasonably foreseeable use
Annex IAnnex I4. Impurities, traces, information about the packaging material
4.1 The purity of the substances and mixtures
4.2 In the case of traces of prohibited substances, evidence for their technical unavoidability
4.3 The relevant characteristics of packaging material, in particular purity and stability
Guidelines on Annex I
COMMISSION IMPLEMENTING DECISION of XXX
on Guidelines on Annex I to Regulation (EC) No 1223/2009 on cosmetic products
http://http://ec.europa.euec.europa.eu//enterpriseenterprise//tbttbt//tbt_repositotbt_repositoryry/EEC186_EN_2_1.pdf/EEC186_EN_2_1.pdf
Guidelines on Annex I4.3 The relevant characteristics of packaging material, in particular purity and stability
• Direct contact with the formulation
• Reference to Regulation on Food Contact Materials (migration)
• Experience with similar formulation/packaging
• Interaction between product and packaging material
• Barrier properties of packaging material
• Composition of the packaging material (+ additives)
• Technically unavoidable impurities
ExampleEyeshadow powder pressed in pan tin plate containing in plastic container
Safety/Technical Sheets Plastic container:
Acrylonitrile Butadiene Styrene (ABS) polymers > 98%> 98%
StyreneStyrene < 0,1% < 0,1% ((FlamFlam. . LiqLiq. 3, Acute . 3, Acute ToxTox. 4, . 4, EyeEye IrritIrrit. . 2, 2, SkinSkin IrritIrrit. 2). 2)
NOT RELEVANTNOT RELEVANT
Safety/Technical Sheets Tin Plate:
Nichel = 800 ppm
ArsenicArsenic = 200 = 200 ppmppm
RELEVANT
Annex IAnnex IPART A – Cosmetic product safety information
6. Exposure to the cosmetic product
7. Exposure to the substances
8. Toxicological profile of the substances
9. Undesirable effects & serious undesirable effects
10. Information on the cosmetic product
RISK ASSESSMENTINGREDIENTS
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
3) EXPOSURE ASSESSMENT
1) HAZARD IDENTIFICATION
2) DOSE- RESPONSE
RISK CARACTERISATION
RISK MANAGEMENT
RISK COMMUNICATION
Little DigressionLittle Digression
HAZARD HAZARD ≠≠ RISKRISKHAZARD:HAZARD: -- POTENTIAL TO CAUSE INJURYPOTENTIAL TO CAUSE INJURY
-- INTRINSIC PROPERTIESINTRINSIC PROPERTIES-- NO RELATION WITH DOSE OR NO RELATION WITH DOSE OR EXPOSUREEXPOSURE
RISK:RISK: -- PROBABILITY OF HARMPROBABILITY OF HARM-- RELATION WITH EXPOSURERELATION WITH EXPOSURE-- EXTENSION TOWARDS SEVERITY EXTENSION TOWARDS SEVERITY
AND NATURE OF HARMAND NATURE OF HARM
POTENTIAL RISK OF A HAZARDOUS SUBSTANCE POTENTIAL RISK OF A HAZARDOUS SUBSTANCE (CYANIDE)(CYANIDE)
CyanideLocked awayLabelled
CyanideAccessibleLabelled
Cyanide inkitchen cupboard
unlabelled
CyanideIn your tea
HazardRisk
POTENTIAL RISK OF A NONPOTENTIAL RISK OF A NON--HAZARDOUS SUBSTANCE HAZARDOUS SUBSTANCE (WATER)(WATER)
HazardRisk
1 LWater/day
3 LWater/day
12 LWater/day
0 LWater/day
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
1) HAZARD 1) HAZARD IDENTIFICATION IDENTIFICATION
2) DOSE2) DOSE‐‐ RESPONSERESPONSE3) EXPOSURE 3) EXPOSURE ASSESSMENTASSESSMENT
RISK CARACTERISATIONRISK CARACTERISATION
RISK MANAGEMENTRISK MANAGEMENT
RISK COMMUNICATIONRISK COMMUNICATION
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
1) HAZARD 1) HAZARD IDENTIFICATION IDENTIFICATION
•• CAN X CAUSE ADVERSE HEALTH EFFECT?CAN X CAUSE ADVERSE HEALTH EFFECT?•• BASED ONBASED ON
‐‐ EPIDERMIOLOGICAL STUDIESEPIDERMIOLOGICAL STUDIES‐‐ CLINICAL STUDIESCLINICAL STUDIES‐‐ IN VIVO STUDIESIN VIVO STUDIES‐‐ IN VITRO STUDIESIN VITRO STUDIES‐‐ QSARQSAR
INTRINSICINTRINSIC
PROPERTIESPROPERTIES
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
2) DOSE2) DOSE‐‐ RESPONSERESPONSE
•• WHAT IS RELATIONSHIP BETWEEN DOSE & WHAT IS RELATIONSHIP BETWEEN DOSE & INCIDENCE/SEVERITY of ADVERSE HEALTH EFFECT?INCIDENCE/SEVERITY of ADVERSE HEALTH EFFECT?
•• WHAT IS DOSE NECESSARY WHAT IS DOSE NECESSARY toto CAUSE HARM?CAUSE HARM?
•• NOAEL (NOAEL (No Observed Adverse Effect Level)
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
NOAEL (NOAEL (No Observed Adverse Effect Level)The highest administered dose of a substance for which no visible change in the morphology, functional capacity, growth of the organism
•• The The outcomeoutcome of long of long termterm toxicitytoxicity (28 (28 –– 90 90 daysdays))The NOAEL The NOAEL shouldshould bebe expressedexpressed asas mg/kg mg/kg bwbw/day /day
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
3) EXPOSURE 3) EXPOSURE ASSESSMENTASSESSMENT
WHAT IS AMOUNT & TIME of EXPOSURE
Dose Dose exposureexposure
SkinSkin exposureexposure
PercutaneousPercutaneous absorptionabsorption
SEDSEDSystemicSystemic ExposureExposure DosageDosage of a of a cosmeticcosmetic ingredientingredient
CALCULATION OF EXPOSURE DOSECALCULATION OF EXPOSURE DOSEAmount applied on skin or mucous membrane, expressed:Amount applied on skin or mucous membrane, expressed:‐‐ weightweight‐‐ weight per body weight (ex: mg/kg weight per body weight (ex: mg/kg bwbw))‐‐ weight per unit of surface (ex: mg/cmweight per unit of surface (ex: mg/cm2 2 of skin)of skin)
a case a case byby case case approachapproach consideringconsidering::Class of Class of cosmeticcosmetic productproductMethodMethod of of applicationapplicationFrequencyFrequency of of applicationapplicationConsumer target Consumer target groupgroupSite of contactSite of contactDurationDuration of contactof contactConcentrationConcentration of of ingredientsingredients in the in the productproductForseeableForseeable misusemisuse
EstimationEstimation of of consumersconsumers’’ exposureexposure toto the the finishedfinished productproduct
Data Data providedprovided byby CosmeticsCosmetics EuropeEurope (ex (ex ColipaColipa))
4 4 mainmain typestypes::
OralOral hygenehygene and care and care productsproducts
EyeEye productsproducts
LeaveLeave on on productsproducts
RinseRinse off off productsproducts
PartitionPartition coefficientcoefficient::takestakes intointo account account rinsingrinsing off and off and diluitiondiluition of of finishedfinished productsproducts bybyapplicationapplication on on wetwet skinskinEx: Ex: ToothpasteToothpaste
RetentionRetention coefficientcoefficient::takestakes intointo account the account the residualresidual partpart of of finishedfinished productsproducts in direct contact in direct contact withwithskinskinEx: ShampooEx: Shampoo
ORAL HYGENE PRODUCTSORAL HYGENE PRODUCTS
ProductProducttypetype
Total Total amountamount per per applicationapplication
(g)(g)
FrequencyFrequency of of applicationapplicationper day per day
PartitionPartition
(%)(%)ExposureExposureper dayper day
(g)(g)
1717 0.480.48ToothpasteToothpaste 1.401.40 22
MouthwashMouthwash 10.0010.00 33 1010 3.003.00
LipstickLipstick 0.010.01 44 100100 0.040.04
TotalTotal 3.523.52
EYE PRODUCTSEYE PRODUCTS
ProductProduct typetype Total Total amountamountper per applicationapplication
(g)(g)
FrequencyFrequency of of applicationapplicationper day per day
PartitionPartition
(%)(%)ExposureExposureper dayper day
(g)(g)
EyeEye makemake‐‐upup 0.0100.010 22 100100 0.0200.020
MascaraMascara 0.0250.025 11 100100 0.0250.025
LinerLiner 0.0050.005 11 100100 0.0050.005
TotalTotal 0.0500.050
LEAVE ON PRODUCTSLEAVE ON PRODUCTS
ProductProduct typetype Total Total amountamountper per applicationapplication
(g)(g)
FrequencyFrequency of of applicationapplicationper day per day
PartitionPartition
(%)(%)ExposureExposureper dayper day
(g)(g)
Face Face creamcream 0.80.8 22 100100 1.601.60
GeneralGeneral creamcream 1.21.2 22 100100 2.402.40
Body Body lotionlotion 8.08.0 11 100100 8.008.00
DeodorantDeodorant((rollroll on)on)
0.50.5 11 100100 0.500.50
HairHair stylingstyling 55 22 1010 11
TotalTotal 13.5013.50
RINSE OFF PRODUCTSRINSE OFF PRODUCTSProductProduct typetype Total Total amountamount
per per applicationapplication
(g)(g)
FrequencyFrequency of of applicationapplicationper day per day
PartitionPartition
(%)(%)ExposureExposureper dayper day
(g)(g)
MakeMake up up removerremover
0.0100.010 22 100100 0.0200.020
ShowerShower gelgel 0.0250.025 11 100100 0.0250.025
ShampooShampoo 8.08.0 11 11 0.080.08
HairHair conditionerconditioner 14.014.0 0.280.28 11 0.040.04
TotalTotal 0.720.72
MaximalizedMaximalized globalglobal dailydaily exposureexposure
Total Total oraloral hygenehygene productsproducts 3.52 g3.52 g
Total Total eyeeye productsproducts 0.05 g0.05 g
Total Total leaveleave on on productsproducts 13.50 g13.50 g
Total Total rinserinse off off productsproducts 0.72 g0.72 g
MaximumMaximum DailyDaily ExposureExposure 17.79 g17.79 g
CALCULATION DAILY EXPOSURE DOSE OF CALCULATION DAILY EXPOSURE DOSE OF SUBSTANCE APPLIED TO THE SKIN (I)SUBSTANCE APPLIED TO THE SKIN (I)
II (mg/day) =(mg/day) == = AA (g/(g/applicationapplication) x 10) x 103 3 (mg/g) x (mg/g) x CC (%) x 10(%) x 10--22 x x FF (day(day--11))
WhereWhere::A A (g) = (g) = AmountAmount of of finishedfinished productproduct appliedapplied//applicationapplication
C C (%) = (%) = ConcentrationConcentration of of ingredientingredient
F F (day(day--11) = ) = FrequencyFrequency of of applicationapplication of the of the substancesubstance
SKIN ABSORPTIONSKIN ABSORPTIONSkinSkin exposureexposure: : amountamount of of substancesubstance in contact in contact withwith anan unitunit area of area of skinskin forfor a a defineddefined periodperiod of of timetime
PercutaneousPercutaneous absorptionabsorption: : passagepassage of of substancesubstance acrossacross the the skinskin withoutwithout indicationindication of of itsitsfatefate
PenetrationPenetration
PermeationPermeation
ResorptionResorption
PERCUTANEOUS ABSORPTIONPERCUTANEOUS ABSORPTION
ReportedReported ad ad absoluteabsolute amountamount of of substancesubstance penetratingpenetrating the the skinskin after a after a certaincertain periodperiod ((μμg/cmg/cm22))
ReportedReported asas a a percentagepercentage of of subtancesubtancepenetratingpenetrating the the skinskin
SEDSEDAmountAmount expectedexpected toto enterenter the the bloodblood streamstream
SED = mg/SED = mg/kg kg bwbw/day/day
MeanMean body body weightweight = 60 kg (= 60 kg (commonlycommonly acceptedaccepted))
CALCULATION (SED)CALCULATION (SED)
SED =SED =(mg/kg (mg/kg bwbw/day)/day)
I I (mg/day) x (mg/day) x DADApp(%) x 10(%) x 10‐‐22
60 kg 60 kg bwbw
WhereWhere II ((µµg/ day) = g/ day) = DailyDaily exposureexposure toto the the substancesubstance
DApDAp (%) = (%) = DermalDermal absorbtionabsorbtion of of substancesubstance in in percentagepercentage
CALCULATION (SED)CALCULATION (SED)
SED =SED =(mg/kg (mg/kg bwbw/day)
DADAaa ((µµg/ cmg/ cm22) x 10) x 10‐‐3 3 (mg/ (mg/ µµg) x SSA (cmg) x SSA (cm‐‐22) x F (day) x F (day‐‐11))
/day) 60 kg 60 kg bwbw
DADAaa ((µµg/ cmg/ cm22) = ) = DermalDermal absorptionabsorption of of substancesubstance asas amountamount ((µµg/ cmg/ cm22))
SSA (cmSSA (cm22) = ) = SurfaceSurface skinskin area area expectedexpected toto bebe in contact in contact withwith cosmeticcosmeticproductproduct
60 kg 60 kg bwbw = = DefaultDefault humanhuman body body weightweight
F (dayF (day‐‐11) = ) = FrequencyFrequency of of applicationapplication of the of the substancesubstance
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
1) HAZARD 1) HAZARD IDENTIFICATION IDENTIFICATION
2) DOSE2) DOSE‐‐ RESPONSERESPONSE3) EXPOSURE 3) EXPOSURE ASSESSMENTASSESSMENT
RISK CARACTERISATIONRISK CARACTERISATION
RISK MANAGEMENTRISK MANAGEMENT
RISK COMMUNICATIONRISK COMMUNICATION
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
RISK CHARACTERISATION
•• Data on INGREDIENTData on INGREDIENT
IrritationIrritation SensibilizationSensibilization, , etcetc
MoSMoS calculationcalculation
•• WHAT IS THE NATURE OF IT?WHAT IS THE NATURE OF IT?
•• IMPORTANCE OF VARIABILITY, UNCERTAINITYIMPORTANCE OF VARIABILITY, UNCERTAINITY
CALCULATION OF THE MARGIN OF SAFETY CALCULATION OF THE MARGIN OF SAFETY ((MoSMoS))
NOAEL (mg/ Kg NOAEL (mg/ Kg bwbw/ day)/ day)MarginMargin of of safetysafety ==
SED (mg/ kg SED (mg/ kg bwbw/ day)/ day)
MoSMoS nevernever belowbelow 100100
Risk characterisation usually involves an expert ……. followed bycalculation of an uncertainty factor or ‘margin of safety’ (MoS). Thiscalculation depends on the systemic exposure to the substance and itstoxicological parameters.
The omission of these steps must be duly justified.
4.04.0 2.52.5 3.23.2 3.23.2
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
1) HAZARD 1) HAZARD IDENTIFICATION IDENTIFICATION
2) DOSE2) DOSE‐‐ RESPONSERESPONSE3) EXPOSURE 3) EXPOSURE ASSESSMENTASSESSMENT
RISK CARACTERISATIONRISK CARACTERISATION
RISK MANAGEMENTRISK MANAGEMENT
RISK COMMUNICATIONRISK COMMUNICATION
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESSRISK MANAGEMENT
• Restriction:concentration of one ingredientFrequency or applied amount
• Full authorisation without limits and restrictions
• Not to go/Withdrawal from the market
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESS
1) HAZARD 1) HAZARD IDENTIFICATION IDENTIFICATION
2) DOSE2) DOSE‐‐ RESPONSERESPONSE3) EXPOSURE 3) EXPOSURE ASSESSMENTASSESSMENT
RISK CARACTERISATIONRISK CARACTERISATION
RISK MANAGEMENTRISK MANAGEMENT
RISK COMMUNICATIONRISK COMMUNICATION
RISK ASSESSMENT PROCESSRISK ASSESSMENT PROCESSRISK COMMUNICATION
• Warning on the label‐ avoid eye contact‐ do not apply on irritated skin‐ etc
COSMETIC SAFETY REPORTCOSMETIC SAFETY REPORTInclude- Hazard data/information related to ingredients, manufacture process, packgaging, chemical & microbiological contaminations….- Quantify SED for product & ingredients- Quantify & evaluate RISK related to use
Combination of all these parametrs
SAFETY TESTSSAFETY TESTSStability (accelerated, centrifuge, etc)Microbiological (Count, Challenge)Tollerability
* Patch-test, HRIPT* Repeated Arm-Wash Test* Het-cam Tests* In-use test
UVA & SPF ???ISPE srl
PATCHPATCH‐‐TESTTESTIrritationIrritation potentialISPE srl potential
Open, OcclusiveSingle/Multi-application (24/48 h, 4 d, 21 d)Product diluted or notNormal / Sensitive skin ⇒ Baby
Clinical Evaluation/ParametersErythema, Edema, Desquamation, Burning Sensation, Itchimg
HUMAN REPEATED INSULT HUMAN REPEATED INSULT PATCHPATCH‐‐TESTTEST
Sensitization PotentialISPE srl
Sensitization PotentialOcclusiveMulti-application
Induction phase (48/72 h, 2 weeks)Challenge phase (after 2 wks, 72 h)
25 volunteersMaximization Grading (n° positive)UV-exposure ⇒ photo-sensitization
REPEATED ARMREPEATED ARM‐‐WASH TESTWASH TESTCleansing productCleansing product
4-5 wash/dayProduct vs SLES vs Tape waterpH, TEWL, Skin colour;Influenced by Temp. & Hardness water
ISPE srl
HETHET‐‐CAM TESTCAM TESTEyeEye‐‐Mucous ProductISPE srl Mucous Product
chorioallantoic membrane offertilised chicken eggs
Control solution (SLES, Sodium Laureth 8-Sulfate, Magnesium Laureth Sulfate, Magnesium Laureth 8-Sulfate, Sodium Oleth Sulfate, Magnesium Oleth Sulfate at 5% active substance)
Q-value (irritation time for adverse reaction)
UVA UVA ‐‐ SPFSPF
SAFETY
or
EFFICACY / CLAIM
EFFICACY
&
CLAIM SUBSTANTIATION
CLAIM = SAFETYCLAIM = SAFETY
UVA & SPFSENSITIVE SKINBaby product
CLAIMCLAIMArticle 20
Product claims1. In the labelling, making available on the market and advertising of cosmetic products, text, names, trade marks, pictures and figurative or other signs shall not be used to imply that these products have characteristics or functions which they do not have.
Little DigressionLittle Digression
Clarification/Explication ?Clarification/Explication ?Article 7a, paragraph g (Directive 76/768)Article 7a, paragraph g (Directive 76/768)
proof of the effect claimed for the cosmetic product, proof of the effect claimed for the cosmetic product, where justified by the nature of the effect or where justified by the nature of the effect or product;product;
DirectiveDirective 87/357/EEC87/357/EEC on the on the approximationapproximation of the of the lawslaws of the of the MemberMember StatesStates concerningconcerning productsproductswhichwhich, , appearingappearing toto bebe otherother thanthan theythey are, are, endangerendanger the the healthhealth or or safetysafety of of consumersconsumers
NOT ONLY COSMETICSNOT ONLY COSMETICS
Clarification/Explication ?Clarification/Explication ?Directive 2005/29/ECDirective 2005/29/EC concerning unfair businessconcerning unfair business‐‐
toto‐‐consumer commercial practicesconsumer commercial practicesNOT ONLY COSMETICSNOT ONLY COSMETICS
Directive 2006/114/ECDirective 2006/114/EC concerning misleading and concerning misleading and comparative advertisingcomparative advertising
NOT ONLY COSMETICSNOT ONLY COSMETICS
Manual on the scopeManual on the scope of application of the Directive of application of the Directive 76/768/EEC 76/768/EEC ‐‐ VERSION 8.0 (JUNE 2011)VERSION 8.0 (JUNE 2011)
ExampleExampleManual for application 76/768/EECManual for application 76/768/EEC
Question: Are products that plump up the lips cosmetic Question: Are products that plump up the lips cosmetic products?products?
Answer:Answer: …… make lips more voluminous may make lips more voluminous may …… fulfill the fulfill the definition of cosmetic products definition of cosmetic products …… placed in contact with the placed in contact with the lips lips ““with a view to exclusively or mainly changing their with a view to exclusively or mainly changing their appearanceappearance””
HoweverHowever, , …… may also meet the definition of medicinal may also meet the definition of medicinal products products ““by virtue of functionby virtue of function””, , …… to to ““restoring, correcting restoring, correcting or modifying physiological functions by exerting a or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to pharmacological, immunological or metabolic action, or to making a medical diagnosismaking a medical diagnosis””
ExampleExampleManual for application 76/768/EECManual for application 76/768/EEC
…… if these products act through if these products act through inflammationinflammationand/or and/or irritationirritation (e.g. products containing (e.g. products containing capsaicincapsaicin), the deliberate induction of a swelling ), the deliberate induction of a swelling effect could be perceived as a significant effect could be perceived as a significant modification of one or more physiological modification of one or more physiological functions in the lips, thus bringing the functions in the lips, thus bringing the products products under the definition of medicinal productsunder the definition of medicinal products..
Clarification/Explication ?Clarification/Explication ?EU RecommendationEU Recommendation 22 September 2006 on the 22 September 2006 on the
efficacy of sunscreen product and their labellingefficacy of sunscreen product and their labelling
EU RecommendationEU Recommendation 7 June 2006 7 June 2006 ⇒⇒ claim on claim on animal testinganimal testing
…… manufacturer and his suppliers have not carried out or commissioned any animal tests on the finished product, or its prototype or any of the ingredients contained in it, or used anyingredients that have been tested on animals by others for the purpose of developing new cosmetic products.
Criteria & GuidelinesCriteria & Guidelines
EU Commission TimingEU Commission Timing
Adoption of the guidelines for criteria Adoption of the guidelines for criteria ⇒⇒ 20122012
Market surveillance/monitoring Market surveillance/monitoring ⇒⇒ 20122012‐‐20152015
Report to EU Parliament Report to EU Parliament ⇒⇒ 20162016
Regulation for claimsRegulation for claimsCOMMISSION REGULATION (EU) No 655/2013COMMISSION REGULATION (EU) No 655/2013
of 10 July 2013of 10 July 2013
laying down common criteria for the justification of laying down common criteria for the justification of claims used in relation to cosmetic productsclaims used in relation to cosmetic products
++Guidelines to Commission Regulation (EU) No 655/2013
Annex IIBest Practice
Annex IFurther description of criteria
CriteriaCriteria
1. Legal compliance
2. Truthfulness
3. Evidential support
4. Honesty
5. Fairness
6. Informed decision‐making
1. Legal Compliance1. Legal ComplianceRegulation:
(1) Claims that indicate that the product has been authorised or approved by a competent authority within the Union shall not be allowed
Guidelines – Annex I:
… since a cosmetic product is allowed on the Union market without any governmental approval. Equally, a CE‐mark shall not be applied on cosmetic products as this would make the consumer think that they are under a regulatory regime different from the Cosmetic Product Regulation
Annex IIAnnex IIBest practice for claim substantiation evidence
Best practices applying to experimental studies (in silico, in vitro, ex‐vivo, etc)
⇒ Similar to “Colipa guidelines ‐ Efficacy Evaluation of Cosmetic Products”
Best practice applying to consumer perception tests
Best practice applying to the use of published information
EXAMPLEEXAMPLEDOES NOT CONTAIN…
FREE- OF…A) ‘contrary to product X, this product does not contain ingredient Y which is known to be irritating’
B) ‘Well tolerated as it does not contain mineral oils’
C) ‘Low in allergens because without preservatives’
Lacking of FAIRNESS
PARABEN FREE ?SILICON FREE ?
ETHOXYLATED FREE ?
PROPYLEN GLYCOL FREE ?
EFFICACY TESTSEFFICACY TESTS
ISPE srl
OUR CRITERIAOUR CRITERIACertified ISO 9001:2008Certified ISO 9001:2008
Member of Order of Research Laboratories of the Member of Order of Research Laboratories of the Ministry of University & Scientific ResearchMinistry of University & Scientific Research
ININ‐‐VIVO, INVIVO, IN‐‐VITRO, SENSORIAL TESTSVITRO, SENSORIAL TESTS
ETHICAL REQUIREMENTSETHICAL REQUIREMENTS
InclusionInclusion CriteriaCriteria: : ageage, sex, race, , sex, race, skinskin typetype, , etcetc))
NonNon‐‐InclusionInclusion CriteriaCriteria (e.g. (e.g. pregnancypregnancy,,skinskindiseasesdiseases, , etcetc))
EthicalEthical aspectsaspects‐‐ Good Clinical PracticeGood Clinical Practice
‐‐ Declaration of Helsinki Declaration of Helsinki (adverse effects, medical (adverse effects, medical control, etc)control, etc)
‐‐ Subject informedSubject informed
‐‐ Written informed consent (sign)Written informed consent (sign)
‐‐ Respect of privacyRespect of privacy
‐‐ Unwanted effects monitored by competent Unwanted effects monitored by competent technicianstechnicians
‐‐ PaymentPayment
PROTOCOLPROTOCOL
Clinical trials should beClinical trials should bescientifically sound andscientifically sound anddescribed in a clear anddescribed in a clear and
detailed protocol.detailed protocol.
PROTOCOLPROTOCOLEEMCO EEMCO GuidelinesGuidelines
European group of EfficacyEuropean group of EfficacyMeasurement of Cosmetics Measurement of Cosmetics and Other topical productsand Other topical products
THE EUROPEAN COSMETIC, TOILETRY THE EUROPEAN COSMETIC, TOILETRY AND PERFUMERY ASSOCIATIONAND PERFUMERY ASSOCIATION
GuidelinesGuidelines forfor the the evaluationevaluation of the of the EfficacyEfficacy of of CosmeticCosmetic productsproducts
COLIPACOLIPA
ININ‐‐VIVO VIVO EFFICACY TESTS EFFICACY TESTS
&&CLAIM SUBSTANTATIONCLAIM SUBSTANTATION
InstrumentalInstrumental evaluationevaluation of of cosmeticcosmetic efficacyefficacy
BiophysicalBiophysical methodsmethodsNon invasive Non invasive techniquetechnique
InformationInformation aboutabout skinskin structurestructure and and functionfunction
ObjectiveObjective evidenceevidence of of the the cosmeticcosmetic efficacyefficacy
pHpHHydrationHydration
RoughnessRoughness
SebumSebum ElasticityElasticity
specificspecific evaluationevaluationforfor eacheach claimclaim
8686
LENITIVE RESTORINGREPAIRING PROTECTIVE
SOOTHING
EVAPORIMETRY, COLORIMETRY CORNEOMETRY, FLOWMETRY PROFILOMETRY, ECOGRAPHY EXPERIMENTAL MODELS
LIGHTENING ANTI‐DARK SPOTS ANTI‐AGE SPOTS
COLORIMETRY IMAGE ANALYSIS DIGITAL IMAGES
MOISTURIZING HYDRATANT EMOLLIENT SOOTHING
CORNEOMETRYPROFILOMETRY
EVAPORIMETRY, CUTOMETRY D‐SQUAME + COLORIMETRY
FIRMING TONIFYING NOURISHING PLUMPING
CORNEOMETRY CUTOMETRY ECOGRAPHY
CLAIM SUBSTANTATIONCLAIM SUBSTANTATION
ANTI‐AGE ANTI‐WRINKLE REPLENISHING
FILLER EFFECT SMOOTHING, PLUMPING
RESTRUCTURING REDEFINING, REFINISHER REDENSIFYNG
REMODELLING REJUVENATION DECONTRACTING
CORNEOMETRY CUTOMETRY COLORIMETRY FLOWMETRY
PROFILOMETRY ECOGRAPHY
IMAGE ANALYSIS DIGITAL IMAGES
CLINICAL ASSESSMENT
ANTI DARK CIRCLES
ANTI EYEBAGS
IMAGE ANALYSISCOLORIMETRY FLOWMETRY
ECOGRAPHY CLINICAL ASSESSMENT
CLAIM SUBSTANTATIONCLAIM SUBSTANTATION
CLAIM SUBSTANTATIONCLAIM SUBSTANTATION
ANTI‐CELLULITE
CORNEOMETRY CUTOMETRY FLOWMETRY
PROFILOMETRY ECOGRAPHY
IMAGE ANALYSIS CLINICAL ASSESSMENT
ANTI‐ STRETCH MARK
IMAGE ANALYSIS COLORIMETRY ECOGRAPHY CUTOMETRY
PROFILOMETRY IMAGE ANALYSIS
CLINICAL ASSESSMENT
APPLICATIONSAPPLICATIONS
ISPE
HAIR CAREHAIR CARE
PHOTOTRICHOGRAM: PHOTOTRICHOGRAM: TrichoScanTrichoScan
SKIN CARESKIN CARESKIN CARESKIN CARE
CLAIMSCLAIMS
ANTIANTI‐‐DARK SPOTSDARK SPOTS
LIGHTENINGLIGHTENING
WHITENINGWHITENING
AUTOAUTO‐‐TANNINGTANNING
ANTIANTI‐‐COUPEROSECOUPEROSE
LENITIVEISPE srl LENITIVE9494
SKIN COLOUR:SKIN COLOUR:CHROMA METER CRCHROMA METER CR‐‐300300
Xenon light sourceXenon light source
Colour rating system L* a* b* Colour rating system L* a* b* CIELABCIELAB
CIE (CIE (CommissionCommission InternationaleInternationale de lde l’’EclairageEclairage))
L* = luminosity, brightness, radiance, shining L* = luminosity, brightness, radiance, shining
(from 0 = black to 100 = white)(from 0 = black to 100 = white)
a*= a*= redred‐‐ green green axisaxis ((‐‐60 +60)60 +60)
b*= blueb*= blue‐‐ yellow yellow axisaxis ((‐‐60 +60) 60 +60)
AntiAnti‐‐wrinklewrinkle//AntiAnti‐‐ageingageing teststests::
SkinSkin hydrationhydration
SkinSkin elasticityelasticity
skinskin roughnessroughness
SkinSkin density density
SkinSkin colourcolourMacrotopographyMacrotopographyClinicalClinical assessmentassessment
SkinSkin roughnessroughness: : SkinSkin replica and replica and ImageImage analysisanalysis
SkinSkin surfacesurface analysisanalysisand and quantificationquantification of of wrinkleswrinkles
Negative imprints of skin surface: Negative imprints of skin surface: fast hardening synthetic polymer fast hardening synthetic polymer and adhesive disksand adhesive disks
T0T0T0
T30
T60
SKIN REPLICASKIN REPLICAof of crowcrow’’s s feetfeet
Silicone replica is illuminated and skin Silicone replica is illuminated and skin furrows are translated into shadows. furrows are translated into shadows.
Image Processing Software (Image Processing Software (QuantilinesQuantilines, , MonadermMonaderm))
SkinSkin roughnessroughness: : PRIMOS PICO OpticalPRIMOS PICO Optical 3 D system3 D system
threethree‐‐dimensional images of the skin surface using dimensional images of the skin surface using a digital stripe projectiona digital stripe projection
25 year old 51 year old25 year old 51 year old20 MHz 20 MHz
skinskin density/density/eechogenicitychogenicity throughthrough
ultrasounds ultrasounds echographyechographyDERMASCAN DERMASCAN CC®® Ver.Ver. 3, 3, CortexCortex TechTech
ClaimsClaimsplumpingplumping, , densifyingdensifying, , nourishingnourishing
SkinSkin hydrationhydrationCORNEOMETER CM 825CORNEOMETER CM 825
GradientGradient in the in the hornyhorny layerlayerPhysicalPhysical principleprinciple: : condensercondenserElectrodeElectrode + upper + upper skinskin = = capacitorcapacitorEpidermalEpidermal capacitancecapacitanceReliableReliable ‐‐ reproduciblereproducible measurementsmeasurementsunder standard under standard conditionsconditions ((TT°°, , rhrh))ArbitraryArbitrary unitsunits
SkinSkin elasticityelasticityCutometerCutometer C&KC&K
measuresmeasures the the viscoelasticviscoelasticpropertiesproperties of the of the skinskin
VerticalVertical deformationdeformationof the of the skinskin intointo the the probeprobe
ClaimsClaimsFirmingFirming, , tonifyingtonifying, , nourishingnourishing
BODY CAREBODY CARE
BODY CAREBODY CARE
CelluliteCelluliteDERMASCAN DERMASCAN CC®® Ver.Ver. 3, 3, CortexCortex TechTech
Before AfterBefore After
Cellulite Cellulite = excess subcutaneous fat bulges into the dermis = excess subcutaneous fat bulges into the dermis ‘‘herniationherniation of the of the dermodermo hypodermal junctionhypodermal junction’’ (in red in the (in red in the
images). images). PProduct application = decrease in the length of roduct application = decrease in the length of dermodermo‐‐hypodermal junctionhypodermal junction (linearization).(linearization).
PerifluxPeriflux PF4001PF4001
Blood microBlood micro‐‐flow measured by flow measured by
computerized computerized
Laser Doppler deviceLaser Doppler device
DIGITAL IMAGESDIGITAL IMAGES
BEFORE APPLICATION 60 DAYS AFTER APPLICATION
SkinSkin surfacesurface: : stretchstretch‐‐marksmarks: : PRIMOS PICO OpticalPRIMOS PICO Optical 3 D system3 D system
threethree‐‐dimensional images of the skin surface using dimensional images of the skin surface using a digital stripe projectiona digital stripe projection
Volume Volume evaluationevaluation: : ScarsScars and and KeloidsKeloidsPRIMOS PICO OpticalPRIMOS PICO Optical 3 D system3 D system
BEFORE BEFORE AFTER AFTER
DEODORANT EFFICACYDEODORANT EFFICACYSNIFF TESTSNIFF TEST
MAKE UPMAKE UP
WITHOUT MASCARAWITHOUT MASCARA WITH MASCARA WITH MASCARA 3.55 mm3.55 mm 4.08 mm4.08 mm
MASCARA: LENGTHENINGMASCARA: LENGTHENING EFFECTEFFECT
distance between rima palpebrarum (eyelash insertion on the upper eyelid) and point of maximum length of the eyelashes.
WITHOUT MASCARAWITHOUT MASCARA WITH MASCARA WITH MASCARA
MASCARA: CURLINGMASCARA: CURLING EFFECTEFFECT
The length of the radius is inversely correlated to the eyelashes curvature: the higher the curvature, the smaller the radius.The curling effect is proved by an increase in the values of the
curvature.
WITHOUT MASCARAWITHOUT MASCARA WITH MASCARA WITH MASCARA
MASCARA: VOLUMIZING EFFECTMASCARA: VOLUMIZING EFFECT
The volumizing effect is proved by an increase in the values of the surface occupied by the eyelashes.
SUNSCREENSSUNSCREENSSUN PRODUCTSSUN PRODUCTS
UVB PROTECTION FACTORUVB PROTECTION FACTORININ‐‐VIVO VIVO ‐‐ SPF SPF
INTERNATIONAL STANDARD INTERNATIONAL STANDARD ISO ISO 24444:201024444:2010
WATER RESISTANT TESTWATER RESISTANT TEST
ColipaColipa GuidelinesGuidelines forfor evaluatingevaluating SunSunProductProduct Water Water ResistanceResistance 20052005
ColipaColipa nn°° 1616Water Water ResistanceResistance labellinglabelling, , 20062006
ISPE srl
ININ‐‐VITROVITRO
BOOTS STAR RATING 2011BOOTS STAR RATING 2011
SUN PROTECTION FACTOR EVALUATION SUN PROTECTION FACTOR EVALUATION DIFFEY and ROBSON + DIFFEY and ROBSON + DIN 67502DIN 67502
ININ‐‐VITRO UVA PROTECTION EVALUATION VITRO UVA PROTECTION EVALUATION UVAPF and Critical Wavelength METHOD ISO UVAPF and Critical Wavelength METHOD ISO
24443 2012 24443 2012
ConsumerConsumer’’s Evaluations Evaluation
It evaluates the consumerIt evaluates the consumer’’s perception s perception of product efficacy of product efficacy
Realistic inRealistic in‐‐use tests useful for analysing concepts, use tests useful for analysing concepts, colours, packaging, acceptance, colours, packaging, acceptance, texturetexture, , fragrancefragranceand and expectationsexpectations..
ISPE
IntensityIntensity levellevel nn°° answersanswers score %score %
VeryVery efficientefficient 11 5%5%
FairlyFairly efficentefficent 99 45%45%
NotNot veryvery efficientefficient 99 45%45%
NotNot at at allall efficientefficient 11 5%5%
NOT AT ALL 5%
FAIRLY45%
VERY5%
NOT VERY45%
ConsumerConsumer’’s Evaluations Evaluation
SENSORY ANALYSISSENSORY ANALYSIS
MEASURE OFMEASURE OF
PLEASANTNESS
ACCEPTABILITY
SENSORY PERCEPTIONS
DEFINITIONDEFINITION
Scientific discipline used to measure Scientific discipline used to measure and analyse the human responses to and analyse the human responses to properties of materials as they are properties of materials as they are perceived by the perceived by the sensessenses
SensorySensory PanelPanel
group of people trained togroup of people trained to
detect and quantify detect and quantify
sensory perceptions sensory perceptions
ISPE
SensorySensory profileprofile
02468
10Consistency
SpreadabilityAbsorption
A B C
ISPE
AccordingAccording toto ourour experienceexperience
best best resultresult isis obtainedobtained
byby employingemploying a a combinationcombination
of of techniquestechniques: :
instrumentalinstrumental test, test,
clinicalclinical assessmentsassessments, , sensorysensory and and subjectivesubjective teststests..
ISPE srl
Final Final reportreportProduct & sponsor Product & sponsor identifications identifications Study designStudy designMethod & devicesMethod & devicesStatistical analysisStatistical analysisResults: tables and Results: tables and graphs graphs SignsSignsBibliographyBibliographyISPE srl
““A fool with a tool is always a A fool with a tool is always a foolfool””
A. Kligman
Thank you!Thank you!