safety efficacy of cosmetics -...

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

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?�uri=OJ:L:2009:342:0059:0209:en:PDF

http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?�uri=OJ: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


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


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

http://ec.europa.eu/enterprise/tbt/tbt_repository/EEC186_EN_2_1.pdf

http://ec.europa.eu/enterprise/tbt/tbt_repository/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


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


3) EXPOSURE ASSESSMENT

1) HAZARD IDENTIFICATION

2) DOSE- RESPONSE

RISK CARACTERISATION

RISK MANAGEMENT

RISK COMMUNICATION

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


1) HAZARD 1) HAZARD IDENTIFICATION IDENTIFICATION

2) DOSE2) DOSE‐‐ RESPONSERESPONSE3) EXPOSURE 3) EXPOSURE ASSESSMENTASSESSMENT

RISK CARACTERISATIONRISK CARACTERISATION

RISK MANAGEMENTRISK MANAGEMENT

RISK COMMUNICATIONRISK COMMUNICATION



•• 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


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)


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


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)


PartitionPartition


(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)


PartitionPartition


(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)


PartitionPartition


(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 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 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 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.

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



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!

safety efficacy of cosmetics -...

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