1. RIGHT SOLUTIONS · RIGHT PARTNER 1 Cosmetics and Sunscreens – Analytical Testing Requirements Scott Colbourne – Business Manager NSW ALS Pharmaceutical Australia

2. RIGHT SOLUTIONS · RIGHT PARTNER 2 Contents Australian Regulations – Testing & Stability requirements ASEAN and EU Regulations – Testing & Stability requirements Typical tests - how and why they are performed? Why validate / re-validate a method?

3. RIGHT SOLUTIONS · RIGHT PARTNER 3 Australian Regulations All ingredients in cosmetic products are regulated as industrial chemicals under the Industrial Chemicals (Notification and Assessment) Act 1989 In addition the Cosmetic Standard 2007 covers certain products If a product’s primary function is as a sunscreen it is regulated by the Therapeutic Goods Administration (TGA)

4. RIGHT SOLUTIONS · RIGHT PARTNER 4 Australian Regulations: Testing of Cosmetics Substances New chemicals applications via NICNAS* : Spectral data to confirm the structural formula Purity Impurities Additives Valid reproducible physico-chemical data, including: – Melting point or boiling point – Specific gravity or density – Vapour pressure – Water solubility – Partition coefficient – Particle size (distribution) or fibre length – Flashpoint, Flammability, Auto-ignition Information from NICNAS Handbook (Appendix F) * Not listed on AICS, Australian Inventory of Chemical Substances

5. RIGHT SOLUTIONS · RIGHT PARTNER 5 Australian Regulations – Testing from Cosmetics Standard 2007 The Cosmetics Standard 2007 describes the requirements for six cosmetic product categories. These categories include various SPF products. The only specific testing noted is SPF: ‘product meets the performance requirements for a broad ‑ spectrum product’

6. RIGHT SOLUTIONS · RIGHT PARTNER 6 Australian Regulations – Sunscreens TGA regulates as therapeutic goods: -Primary sunscreens - SPF 4 or more -Moisturisers containing sunscreen with SPF >15 Sunscreens must comply to ARGS (Australian Regulatory Guidelines for Sunscreens) Efficacy of each sunscreen product is to be tested to determine the sun protection factor (SPF)

7. RIGHT SOLUTIONS · RIGHT PARTNER 7 Australian Regulations – Testing Sunscreens Stability (ARGS 7.1) The data must substantiate the physical, chemical and microbiological stability of the product for at least the claimed shelf life Stability data is not required to be submitted to the TGA for product listing However may be requested for review by the TGA at any time

8. RIGHT SOLUTIONS · RIGHT PARTNER 8 Physical testing (at least): appearance, emulsion stability, absence of crystallisation, odour, viscosity Chemical stability testing (should include): pH, active/s content. Using a validated, stability-indicating analytical procedure (for example, HPLC) Microbiological stability - preservative efficacy testing at the start and end of stability trials Australian Regulations – Testing Sunscreens Stability (ARGS 7.1)

9. RIGHT SOLUTIONS · RIGHT PARTNER 9 Australian Regulations – Testing Sunscreens Stability (ARGS 7.1) Accelerated studies require enough time points to allow statistical analysis as the shelf life is extrapolated E.g. 0, (1 or 2), (3 or 4), (5 or 6), 9 and 12 months Followed by 24 and 30 months as required

10. RIGHT SOLUTIONS · RIGHT PARTNER 10 Australian Regulations – Testing Sunscreens Quality Control (ARGS 8.2) Where a specific monograph from the pharmacopoeia is available (BP, Ph Eur or USP-NF), it must be used: This applies to most ingredients – both organic and inorganic In addition many of the excipients (including solvents) used in sunscreen products are also available Finished products are not the subject of monographs and are therefore controlled by appropriate “in house” quality control “in house” methods cover identity and relevant physical, chemical and microbiological properties. Test methods must be validated, as appropriate.

11. RIGHT SOLUTIONS · RIGHT PARTNER 11 ASEAN Cosmetic Directive – Testing Requirements ARTICLE 9 (Methods of Analysis) The following cosmetic product documents shall be made available to the cosmetic regulatory authority: – methods used by the manufacturer to check the ingredients – the criteria used for microbiological control of cosmetic products chemical purity of ingredients of cosmetic products

12. RIGHT SOLUTIONS · RIGHT PARTNER 12 ASEAN Guidelines – Testing Requirements Appendix VI – ASEAN Guidelines for Cosmetic Good Manufacturing Practice Raw and packaging material specifications should include: – Testing parameters and acceptance limits Bulk and finished product specifications should include : – Physical properties – Chemical assay and/or microbiological assays and their acceptance

13. RIGHT SOLUTIONS · RIGHT PARTNER 13 EU Legislation – Testing Cosmetics Legislation is covered under European Union law (1223/2009). Each product requires a safety report (Annex I) The EU provides a guidelines on Annex I for the cosmetic product safety report Guidelines regarding the testing of cosmetics are taken from the SCCS (Scientific Committee on Consumer Safety)

14. RIGHT SOLUTIONS · RIGHT PARTNER 14 SCCS Notes of Guidance for the EU: Testing Cosmetics Evaluation of new substances includes: – characterisation and purity of the chemical; – characterisation of the impurities or accompanying contaminants; – solubility; – partition coefficient (Log Pow); – additional relevant physical and chemical specifications; – homogeneity and stability; – UV-VIS-absorption spectrum

15. RIGHT SOLUTIONS · RIGHT PARTNER 15 SCCS Notes of Guidance for the EU: Testing Cosmetics Stability and physical & chemical characteristics of the cosmetic product (4-3.3) The physical stability should be established, ensuring no changes in physical state during transport, storage or handling of the product. Relevant stability tests Relevant physical and chemical parameters should be controlled for each batch of the finished product, e.g: – Organoleptic properties – pH – Viscosity

16. RIGHT SOLUTIONS · RIGHT PARTNER 16 SCCS Notes of Guidance for the EU: Testing Cosmetics Guidelines on Microbiological Quality of the Cosmetic Product (4-4) to ensure the microbial safety of cosmetics for the consumer to maintain the quality and specifications intended of the product Quantitative and qualitative Tests (4-4.2) – Total viable count – Pathogens: Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans Challenge testing (4-4.3) – Based on US Pharmacopoeia and European Pharmacopoeia – The efficacy of the cosmetic product’s preservation through challenge testing – assessed during product development

17. RIGHT SOLUTIONS · RIGHT PARTNER 17 Typical Tests - Physical Appearance Identification Viscosity Density (Specific Gravity) Hydroxyl Value: measure of the content of free hydroxyl groups Peroxide Value: initial evidence of rancidity in unsaturated fats and oils (primary oxidation) Anisidine Value: also linked to rancidity (secondary oxidation) Saponification Value: how much of the fat will saponify. Can be used as a measure of average molecular weight pH Acidity/Alkalinity – how much base or acid is required to reach a pre- determined pH

18. RIGHT SOLUTIONS · RIGHT PARTNER 18 Typical Tests - Chemical Sunscreen Raw Materials: – Tests dictated in Pharmacopoeia Monographs: -Physical Tests (already covered) -Assay -Impurities Sunscreen Finished Products: Zinc Oxide and Titanium Dioxide – by titration or ICP Sunscreen Actives – generally by HPLC Preservatives – generally by HPLC

19. RIGHT SOLUTIONS · RIGHT PARTNER 19 Typical Tests - Chemical Cosmetics and Raw Materials: – Alcohols – Fatty acids – Essential Oils – Vitamins – Heavy Metals Identification and Assay to assess: -Presence -Purity -Amount in finished product

20. RIGHT SOLUTIONS · RIGHT PARTNER 20 Typical Tests - Microbiological Initial Consumer Safety, Good Manufacturing Process: – General TAMC Yeast and Mould Staphylococcus aureus Pseudomonads Indicator of general hygiene in water, environment, raw materials and finished product Pathogens which are able to affect immunocompromised users, wounds, eyes/ears Pseudomonads can affect appearance – discolouration and phase separation Ongoing Consumer Safety – multiple use cosmetics – Challenge Testing (Preservative Efficacy) The test involves inoculating with micro-organisms to challenge the preservative system Generally tested at 2, 7, 14 & 28 days

21. RIGHT SOLUTIONS · RIGHT PARTNER 21 Method Validation – what is involved? Generally performed for quantitative assays, for actives and preservatives (e.g. sunscreen raw materials and finished products) Linearity / Range – Is the method’s response linear across the required range?

22. RIGHT SOLUTIONS · RIGHT PARTNER 22 Method Validation – what is involved? Precision – If I run the method many times do I get consistent results? Accuracy – Do I get the number I am looking for? Specificity – Is there any interference from another substance? Robustness – How does my method cope to small changes in the parameters?

23. RIGHT SOLUTIONS · RIGHT PARTNER 23 Method Validation and Re-Validation – why? Scenario 1: Excipient B is reduced to 45% and Excipient C increased to 10% Probably not, as the ingredients are the same and the assay should not be affected Scenario 2: Excipient C is replaced by a new Excipient E Yes, the ingredients are different therefore the new excipient may: Affect the extraction of the active from the sample during the method Interfere with the active’s response, giving rise to specificity issues A Sunscreen with the following formulation: – 5% Active A – 50% Excipient B – 5% Excipient C – 40% Excipient D The assay for Active A is validated The sunscreen’s formulation is changed. Is re-validation required? As discussed previously – to ensure the result is Accurate, Precise and Specific To satisfy regulatory requirements

24. RIGHT SOLUTIONS · RIGHT PARTNER 24 References NICNAS Chemical Information - CosmeticsCosmetics Cosmetics Standard 2007 – Australia Cosmetics Standard 2007 TGA Sunscreens – Regulatory Guidelines TGA Sunscreens ASEAN Cosmetics Directive European Union law Regulation 1223/20091223/2009 Guidelines on Annex I to Regulation (EC) No 1223/2009 Guidelines on Annex I SCCS'S Notes of Guidance for the Testing of Cosmetic substances and their safety evaluation - 8th revision SCCS'S Notes of Guidance Draft Guidance for Industry: Cosmetic Good Manufacturing Practices (US FDA) Draft Guidance for Industry: Cosmetic Good Manufacturing Practices