This guideline is currently under review.

The information below should be read in conjunction with the guidelines for the approval of new substances given in the ARGOM section on applications for new substances.

On this page: 10.1 Naming of new substances | 10.2 New active ingredients | 10.3 Safety data requirements for new actives | 10.4 Justification for not providing particular studies | 10.5 Related studies | 10.6 UV spectral characteristics | 10.7 New excipients

10.1 Naming of new substances

A 'Proposed Name for a Chemical Substance Used in a Therapeutic Good' application form needs to be submitted to the TGA to enable the establishment of an identity and an appropriate 'Australian Approved Name' (AAN) for the substance. Information on the naming of substances and applying for an AAN can be found on the TGA Internet site.

There are no fees for the AAN applications and approval of ingredient names (at the time of publication). However, fees will apply to the evaluation of the data for the new substance and for the listing or registration of the product as specified in the summary of fees and charges available from the TGA Internet site.

10.2 New active ingredients

Sponsors wishing to market a product containing an active ingredient which is not on the Therapeutic Goods (Permissible Ingredients) Determination must submit data to establish the safety and efficacy of the ingredient under its proposed conditions of use.

10.3 Safety data requirements for new actives

Table 4 lists the topics of relevant guidelines for the types of safety data that are usually required for a new sunscreen active ingredient or new excipient (see also new excipient section).

The list of relevant European Union (EU) 'non-clinical' guidelines that have been adopted by the TGA can be found on the TGA Internet site. They are not detailed in this Sunscreen Guideline document because there are frequent changes and sponsors should, therefore, consult the current list on the TGA Internet site. These EU guidelines relate to sunscreens because sunscreening products (as defined earlier in this Guideline) are treated as therapeutic goods in Australia.

The intention in listing relevant guideline topics is not to set absolute requirements but to assist sponsors in assessing the type and depth of information needed to support an application with the understanding that primary sunscreen products are treated as therapeutic goods in Australia as opposed to 'cosmetics' in Europe.

If a particular guideline is not applicable or other data are available that adequately address the same criteria, alternative approaches based on adequate scientific justification will be considered by the TGA during evaluation of the application, or pre-submission. Relevant human studies are acceptable in the assessment of potential skin irritation and sensitisation using the repeat 'insult patch test' or other relevant validated tests.

Table 4. Safety data normally required for a new sunscreen active ingredient or excipient. Requirements Photostability UV absorption spectra Acute toxicity (oral and dermal; animal data) Local tolerance: skin irritation (animal data and/or human repeat insult patch test - HRIPT

phototoxicity (animal and/or human data)

eye irritation (animal in vivo or in vitro test) Allergenicity: skin sensitisation (animal data and/or HRIPT)

photosensitisation (animal and/or human data - HRIPT) Toxicokinetics: oral and dermal bioavailability

ADME (absorption, distribution, metabolism and excretion) studies

Note: An in vivo determination of dermal and oral absorption is needed to establish systemic exposure via both routes and to enable interpretation of the toxicity studies. Repeat dose toxicity (oral and dermal) at least 3 months Genotoxicity: In vitro bacterial (Ames) assay

bacterial (Ames) assay In vitro mammalian cell line assay

mammalian cell line assay In vitro and in vivo chromosome aberration assay

and chromosome aberration assay Note: Genotoxicity in vitro testing in bacterial, mammalian cell lines, and chromosome aberration assay should include photomutagenicity arm. Reproductive toxicity Notes: For assessment of developmental and fertility effects. Endocrine disruption potential needs to be addressed. This could be examined during the repeat-dose toxicity and/or reproductive toxicity studies.

Carcinogenicity Note: In vivo carcinogenicity and photocarcinogenicity bioassays or a justification for not providing these studies (see below). Interaction potential Note: Since sunscreen formulations usually contain more than one active ingredient, data on the potential for interaction of the new substance with other UV filters will usually need to be provided.

More details on different safety tests for chemicals for pharmaceutical use can be found at the Internet sites of the following organisations:

The European Medicines Agency

The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)

The Organisation for Economic Co-operation and Development Guidelines for the testing of chemicals (section 4: Health Effects).

More details on different safety tests for chemicals that are for cosmetic sunscreens used in Europe can be found in The SCCS's Note for Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation 7th Revision 14 December 2010 SCCS/1416/11 .

10.4 Justification for not providing particular studies

In circumstances where particular tests specified in the table above (TGA-adopted European guidelines) are not feasible or appropriate, sponsors should submit a justification for not including these tests in the dossier which is based on sound scientific argument.

In the case of in vivo carcinogenicity bioassays, a justification for not including long-term studies could be based around the following issues as they apply to the ingredients or product:

the expected pattern of use

results of in vitro and in vivo genotoxicity assays

and genotoxicity assays lack of similarity to other molecules with known carcinogenic activity

low persistence in the skin

low or no in vivo dermal absorption

dermal absorption lack of photosensitisation or phototoxic potential

proven photostability

lack of possible adverse effects on the skin (change to epidermis/dermis)

length of submitted in vivo repeat dose toxicity studies

repeat dose toxicity studies lack of adverse activity in local tolerance studies (skin irritation and skin sensitisation).

10.5 Related studies

Other studies that are not currently referenced in EU guidelines may be useful in supporting particular applications. Reference to these studies is included only as a guide. They will not be relevant in all cases, nor should they be seen as a complete list of relevant studies. Examples include the following studies and referenced Internet sites which may be useful in providing information on the potential of a substance to cause tumours in people:

studies using appropriate and validated transgenic animal models to test exposure to the substance; information on transgenic models can be found on the OECD or European Centre for the Validation of Alternative Methods (ECVAM) internet sites

in vitro human dermal cell cultures exposed to the substance

human dermal cell cultures exposed to the substance in vitro human dermal tumour cell cultures exposed to the substance.

Additionally, the following references may be useful when investigating the use of ingredients with a potential for skin corrosion/irritation:

Non-animal testing strategies for assessment of the skin corrosion and skin irritation potential of ingredients and finished products; M K Robinson et al ; Food and Chemical Toxicology , 40(5), pp 573–592, 2002.

; , 40(5), pp 573–592, 2002. OECD/OCDE, test number: 431 (April 2004) OECD Guidelines for the testing of chemicals; in vitro skin corrosion: human skin model test.

10.6 UV spectral characteristics

In addition to the requirements stated in the ARGOM chapter on Quality, sponsors should provide data to establish the UV absorption range of the new substance enabling confirmation of UVA/UVB absorption profile. Data addressing the potential for physical interaction with other commonly used sunscreening agents should also be provided.

10.7 New excipients

Where a therapeutic sunscreen contains an excipient ingredient which is not in any product currently included in the ARTG for supply in Australia, the excipient must be assessed for use by the TGA. The following information is required as a minimum:

naming and identification of an ingredient name as an Australian Approved Name (AAN) - this may be finalised while the safety data are being evaluated

identification of the excipient as a substance included in the Personal Care Products Council International Cosmetic Ingredient Handbook (Dictionary) (the page number and reference should be quoted). There is also an on line subscription service known as wINCI that provides an electronic version of INCI monographs

assurance that it does not appear in Annex II to the EEC Directive 76/768 list of substances which must not form part of the composition of cosmetic products

documentary evidence that the excipient has been approved by the appropriate regulatory agency in Sweden, Canada, USA, UK or the Netherlands; or evidence that there have been marketplace sales of comparable products containing the excipient in one of those five countries for at least two years

acute oral toxicity study

skin irritation study - animal or alternative study such as HRIPT

sensitisation study - skin, animal and/or (preferably) HRIPT.

The following additional studies may be requested in individual cases where concern becomes evident at the time of evaluation:

in vitro mutagenicity (for example, an Ames test or other validated alternative test)

mutagenicity (for example, an Ames test or other validated alternative test) eye irritation study (animal in vivo or in vitro test)

or test) in vitro or in vivo percutaneous absorption test.

All of the above information should be submitted for safety evaluation of the new substance for use in therapeutic sunscreens. Additional studies may be requested in individual cases where concerns become evident at the time of evaluation.

Once the substance is approved (and an AAN has been assigned), it will thereafter be able to be used in other therapeutic sunscreens without the need for further evaluation, but only up to the safety limit that has been approved. Any increase in that safety limit requires submission and approval of a formal application. The substance may also be able to be used in other topically applied medicines (subject to any conditions or limitations) without the need for further evaluation. However, additional data may be required if the characteristics of the substance are considered to change in different formulations or patterns of use in new products or if the substance is to be used outside the stated conditions and/or limitations.

Alternative sources of data on the safety of the excipient will be considered. For example, if the excipient has been assessed by NICNAS or by the US Cosmetic Ingredient Review (CIR) group, the review document may be sufficient in itself. Copies of CIR reviews are available from the Internet site www.cir-safety.org. Copies of NICNAS reviews may be available from the supplier of the excipient.

Required study reports should be submitted in full as well as in summary form (as described in the ARGOM Chapter on Applications). Simple summaries or synopses of studies without the full study reports are not acceptable for assessment.

All studies submitted must be in English or be provided with an accompanying English translation.

The EU guidelines that have been adopted by the TGA for therapeutic goods should be referred to for detailed guidance on the appropriate tests and how they should be conducted. Studies can be rejected as 'invalid' if appropriate and scientifically robust methodology is not followed (for example, low animal numbers, lack of or inappropriate controls).

Proper and comprehensive identification of the substance(s) being tested in all studies is required; laboratory codes, trade names and synonyms must be linked to the substance identified in the new substance application form for the AAN.

Concentrations of the new substance used in all studies must be clearly and unambiguously stated. The intended final concentration of the new excipient in therapeutic goods to be marketed in Australia must be stated; this allows a comparison to establish that the submitted studies were conducted at concentrations to support the proposed levels to be used in marketed goods.

Where a substance is present in the product with the listed purpose of excipient, no therapeutic claims can be listed against its presence.

If a substance with a known active function is classified as an excipient, evidence of excipient function and purpose will be required.

Furthermore, a justification must be provided for the inclusion of that substance as an excipient at a concentration in excess of the concentration typically used for its role as an active ingredient. If that concentration is above the approved safety limit for use in listed products, then the product with that concentration of the substance must be registered.

The concentrations of excipients with a known active function in the formulation must be below the concentration associated with its established active function. If the excipient concentration is above the minimum threshold of active function then the substance should not be classified as an excipient in the product but, instead, should be classified as an active substance in the product and it will be evaluated as an active component of the product. In this case a therapeutic sunscreen containing that substance must be listed or registered on the ARTG.