ISO/TC 217 & Analytical Methods for Cosmetics

ISO/TC 217 &

Analytical Methods for Cosmetics

Pr Pierre-Antoine Bonnet

Convener ISO/TC 217 WG3

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Standardization Cosmetics

Why developing standards in cosmetics ?

Why developing ISO standards for analytical methods in cosmetics ?

- To facilitate international trade

- To get the best and safest cosmetic products

- To have common methods between all stakeholders

- To have strong bases for discussion between stakeholders

- To eradicate falsification and bad quality products

For the benefit of all: consumers, producers, traders, regulators

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The main criteria for the development of methods is:

QUALITY for safe and pleasant use

Development of methods to insure the quality of

- the cosmetic products

- the ingredients of the cosmetic products

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Quality of the ingredients and cosmetic products:

Development of analytical methods to:

- confirm the quality

by the assay of impurities, traces

- avoid the occurrence of analytes of concern

Examples of issues: Nitrosamines, Heavy Metals, Phthalates….

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Recurrent international issue: Nitrosamines

ISO standards to avoid

artifacts, false positive results

x

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ISO standards for the best quality products

x

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ISO standards to avoid the presence of unsafe components

x

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ISO standards to get

reliable results

x

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International: ISO (ISO) Technical Committee TC 217

Europe: CEN (EN) Technical Committee TC 392

France: AFNOR (NF) Commission S91K

Edition of: Standards

Technical Specifications (TS)

Technical Reports (TR)

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Different and complementary

Working Groups: WG

WG1 Microbiology

WG3 Analytical Methods

WG4 Terminology

WG6 Good Manufacturing Practices

WG7 Sun Products

WG8 Nanomaterials

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Standardization Cosmetics: Analytical Methods

Analytical Methods

Published Standards:

NF ISO 15819:2008: Cosmetics – Analytical methods –

Nitrosamines: Detection and determination of N-

nitrosodiethanolamine (NDELA) in cosmetics by HPLC-MS


Nitrosamines: Detection and determination of N-

nitrosodiethanolamine (NDELA) in cosmetics by post-column

photolysis and derivatization


Validation criteria for analytical results using chromatographic

techniques

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Standards in progress (ISO):

TR 14000: Cosmetics – Analytical Methods – Nitrosamines:

Technical guidance document on minimising and determining

N-nitrosamines in cosmetics

TR17276: Cosmetics – Analytical approach for screening and

quantification methods for heavy metals in cosmetics

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New Work in Progress NWIP (ISO):

NWIP: Cosmetics – Analytical methods – Validation criteria for

analytical results using non chromatographic techniques

At the TC level, for repartition of WG workload:

NWIP: Cosmetics – Analytical method – Detection and

quantitative determination of Diethanolamine (DEA) by GC/MS

NWIP: Cosmetics – Guideline on the stability testing of

cosmetics products

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How WG3 works for performance verification of the

Analytical methods proposed for Standardization ?

Main approach is by “peer reviews” in experts labs

If problems occur, improvements and performance

verification might lead to interlaboratory tests

m

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Standard ISO 15819:2008

Proposition of revision in 2012

Positive vote for revision on July 2012

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Discussion of first comments in Florianopolis, Oct 2012

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ISO 10130:2010 Standard on Nitrosamines

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ISO10130 further to a collaborative study from CTPA in

Int. J. Cosmetic Sci. 2006

c

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Besides the development of analytical methods for standardization, WG3 develops Technical Reports

TR14000 on minimising Nitrosamines in cosmetics

Report on

- analytical methods (screening to quantitative)

- formulation guidances

for avoidance of the formation of Nitrosamines

Publication awaited in the forthcoming weeks……

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TR17276 on Heavy Metals

Report on available analytical methods

for testing, screening, quantitate

heavy metals in cosmetics and ingredients

first step for the future development of standards

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ISO 12787:2011

Validation criteria for analytical results in cosmetics

Confidence in performance, reliability and quality

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Background and Rationale for ISO12787 standard

Cosmetics are very diverse with an extensive area of various products

perfumes, creams, shampoos, lipsticks, mascara, powders, soaps, toothpastes….

How far can we obtain validation data for a single method to be considered as pertinent and suitable for use for cosmetics, including finished products and ingredients ?

ISO12787 gives a procedure for validation criteria

c

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ISO12787 gives a procedure for validation criteria

for analytical results using chromatographic methods

ISO12787 allows to extend the use of an analytical method known as suitable for a cosmetic matrix to another cosmetic matrix

The ISO12787 standard describes 3 steps

- 1st step: Study on standard solutions

- 2nd step: Screening sample

- 3rd step: Assay

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Aim of ISO12787:

to ensure the sample assay results

ISO12787 is particularly beneficial

- for the determination of analytes in various and complex matrices

(i.e. cosmetics)

- when a full method validation is not appropriate or cannot be achieved (too many different matrix samples to analyze)

- when it is not possible to make reconstituted sample matrices

v

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1st Step: Suitability study using standard solutions

- Determine the quantification limit in solvent

- Check the calibration range linearity

- Check the system conformity

All necessary specificity parameters such as resolution, asymmetry, selectivity..

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2nd Step: Screening

Evaluation of the analyte content (estimated value)

Two cases:

- samples detected without analyte or with analyte content such as the s/n ratio is low

- samples detected with analyte content such as the s/n ratio is > 10

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3rd Step: Assay

Depending the results of the former screening step:

- If no detection: ensure the absence of detection of the analyte depending following cases:

- assays are performed with a target value

- assays are performed without any target value

- If the analyte has been detected - obtain an assay result with different suitable and sufficient validation parameters to ensure its validity

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Example of tests to be performed for results validation

using the 3 steps procedure:

standard solutions, sample screening, assay

Validation criteria

using Standard

solution

Sample

screening

Assays

1st step 2nd step 3rd step Analyte not detected

or with a s/n < LoQ

Analyte detected

with s/n > LoQ Assays with spike

recovery

Assays using a

target value

Solvent standard

calibration levels

5 (LoQ)

+

15 (53) Linearity

5 5

Unspiked samples 1 1 1 1 (3) a Spiked samples

(before treatment)

i.e. PrEMS

3 1 1 (2) a

Spiked sample

(after treatment)

i.e. PoEMS

1

Check standard 1 1 a If a RSD or a confidence interval is to be determined on the final assay result

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Example of application of ISO 12787 standard

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CEN Standards:

EN 16217: Methods for analysis of allergens – Quantification

of suspected fragrance allergens in consumer products. Step

1 – GC analysis of ready to inject samples

Standardization Cosmetics: Analytical Methods Determination of allergens


24 allergens detected and quantified by GC/MS Allergens regulated in the EU


•Coeluted compound

•(Non common ions)

•Rs>1.5

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Standards in final phase (CEN):

prEN 16342: Cosmetics — Analysis of cosmetic products —

Quantitative determination of zinc pyrithione, piroctone olamine and

climbazole in surfactant containing cosmetic anti-dandruff products


Determination of 3-iodo-2-propynyl butylcarbamate (IPBC) in

cosmetic preparations, LC-MS methods


Screening for UV-filters in cosmetic products and quantitative

determination of 10 UV-filters by HPLC

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New Work in Progress (CEN):

NWI: Cosmetics – Analysis of cosmetic products - GC/MS method for

the identification and assay of 12 phthalates in ready to inject

cosmetic samples

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Determination of 12 phthalates

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Cosmetics EU Regulation

In Europe

Annexes to Directive 76/768/CEE and Regulation 1223/2009

lists of ingredients/impurities that are

- forbidden (ex: CMR compounds…)

- or regulated (ex: UV filters, conservatives…)

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European Commission

Seven Directives on Analytical Methods

First Commission Directive 80/1335/EEC of 22 December 1980 on the

approximation of the laws of the Member States relating to methods of

analysis necessary for checking the composition of cosmetic products

[Amended by Directive 87/143/EEC, Official Journal L 383 of 31.12.1980]

Second Commission Directive 82/434/EEC of 14 May 1982

[Amended by Directive 90/207/EEC, Official Journal L 185 of 30.06.1982]

Third Commission Directive 83/514/EEC of 27 September 1983

Fourth Commission Directive 85/490/EEC of 11 October 1985

Fifth Commission Directive 93/73/EEC of 9 September 1993

Sixth Commission Directive 95/32/EC of 7 July 1995

Seventh Commission Directive 96/45/EC of 2 July 1996

http://eur-lex.europa.eu/smartapi/cgi/sga_doc?smartapi!celexplus!prod!DocNumber&lg=en&type_doc=Directive&an_doc=1980&nu_doc=1335









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Discussion at the European level

to actualize the Methods “Directives”

to replace them by Standards

in line with the new Regulation 1223/2009 to

be implemented on July 11, 2013

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Some other good reasons

to develop standardized methods….

Identification of …….

…..”False Medicines”,

presented as cosmetics

…..Cosmetic Falsifications

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Skin whitening products / « false medicines »

Methods for Hydroquinone & corticosteroïdes survey

Hydroquinone Arbutine Acide kojique Acide azélaïque

Clobetasol propionate Fluocinonide Betamethasone dipropionate

Hydroquinone and Corticosteroïdes

are banned in cosmetics in the EU

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Skin whitening products / « false medicines »

Methods for Hydroquinone & corticosteroïdes survey

Corticosteroides Retention time

(min) Unadjusted relative retention

Triamcinolone 3,86 0,42

Prednisolone 4,49 0,49

Cortisone 4,58 0,50

Hydrocortisone 4,65 0,51

Bétaméthasone base

Triamcinolone acetonide

5,52 coeluted

0,60

Dexamethasone

Desonide

5,68 coeluted

0,62

Desoximetasone

Fluocinolone acetonide

6,29 coeluted

0,68

Prednisolone acétate

Flurandrenolide

6,92 coeluted

0,75

Hydrocortisone acétate 7,32 0,80

Hydrocortisone butyrate

Budesonide1

Methylprednisolone acétate

7,98 coeluted

0,87

Betaméthasone acétate 8,33 0,91

Budesonide2

Dexamethasone acétate

9,13 Coeluted with ISTD

1,00

Hydrocortisone valérate

Hydrocortisone aceponate

9,85 coeluted

1,07

Fluocinonide 10,83 1,18

Diflorasone diacétate 11,52 1,26

Betamethasone valerate 11,89 1,30

Amcinonide 12,50 1,36

Difluprednate 13,04 1,42

Prednicarbate 13,74 1,50

Alclometasone dipropionate 14,08 1,54

Halcinonide 14,92 1,63

Mometasone furoate

Betamethasone dipropionate

15,40 coeluted

1,68

Clobetasol propionate 16,30 1,78

Beclomethasone dipropionate 18,93 2,07

Prednisolone hexanoate 20,96 2,29

Flumethasone pivalate 25,10 2,74

Fluocortolone pivalate 27,55 3,01

Difluocortolone valérate 28,56 3,12

Clocortolone pivalate 31,05 3,43

Fluocortolone -hexanoate 37,04 4,05

Butylparaben (ISTD) 9,13 1,00

Development of methods for Hydroquinone,

Hydroquinone esters and corticosteroïdes survey

26/04/2013 – Titre de la présentation

DEG in some falsified/counterfeit Toothpastes

2007

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DEG in some falsified/counterfeit Toothpastes

2007

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ISO WG3 experts

65 experts registered

expertise diversity: industry, regulation, standardization, academy

20 member states: Brazil, Spain, France, USA, India, UK, Germany, Columbia, Japan, Jordan, Korea, Poland, Australia, South Africa, China, Sweden, Sri Lanka, New Zealand, Nigeria, Czech Republik

Regular meetings (2 / year) since 2000 (creation of ISO/TC217)

WG3 meeting in Jeju Fall 2008

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Thanks to KTAS and KCA for the organization of the

2013 ISO TC 217 WG3 meeting in Osong !!!!

Documents

ISO/TC 217 & Analytical Methods for Cosmetics