You are here

TGA Internet site archive

The content on this page and other TGA archive pages is provided to assist research and may contain references to activities or policies that have no current application. See the full archive disclaimer.

Change to requirements for assessing the safety of new excipients in topical non-prescription medicines

26 June 2006

The TGA is introducing a change to existing arrangements for assessing the safety of new excipients in topical non-prescription products from 1 September 2006. From this date, sponsors will be required to provide toxicological data to support the safety of new excipients and have it approved by the TGA before the product is listed or registered, rather than within 6 months after listing or registration.

Existing arrangements

Under existing arrangements sponsors are allowed to include new excipients in topical non-prescription medicines without first having their safety assessed if:

  • The ingredient is named in the International Cosmetic Ingredient Dictionary (ICID);
  • The sponsor gives certain assurances; and
  • The sponsor agrees to provide the required toxicological data within six months of the date of listing/registration of the product.

Details of the existing arrangements are included as Attachment 1. These arrangements have significant disadvantages, as detailed under Reasons for the change (below).

Revised arrangements

From 1 September 2006 sponsors will be required to provide toxicological data to establish the safety of each new excipient in a topical non-prescription medicine before the product is listed or registered, rather than within 6 months of listing or registration.

New ingredient names will be approved as 'Australian Approved Names' (AAN) before the any products containing the ingredient are listed or registered. The use of 'Provisional Approved Names' will be phased out by mid-2007.

No other changes are to be made to any other aspect of the existing arrangements. Evaluation fees, application forms, data requirements, labelling and all other requirements will remain exactly as they are at present.

This change will allow the TGA to ensure that new excipients are safe before they become available in products for use by consumers. The change will be reflected in amendments to Chapter 10 of the Australian Regulatory Guidelines for OTC Medicines (ARGOM), effective from 1 September 2006.

Background information

A consultation paper was published on the TGA web site in November 2005. Following requests from industry stakeholders a more detailed consultation paper was sent to industry associations in January 2006.

Comments were received from the Australian Self-Medication Industry (ASMI), Advocate for the Consumer, Cosmetic, Hygiene and Specialty Products Industry (ACCORD), and the Complementary Healthcare Council of Australia (CHC).

The ASMI advised general support for the proposed change but supported greater self regulation for low risk substances. ACCORD and CHC opposed the change, supporting a greater degree of self regulation for low risk substances.

In addition, ACCORD advocated mutual recognition of assessments between the chemicals and medicines regulators and a similar risk management approach to low risk substances for chemicals and medicines. The CHC pointed to what they saw as problems with the administration of current policy and proposed an alternative scheme based on certification of a limited range of information and self-certification as to safety.

The TGA is willing to consider and discuss all of these issues, particularly in the context of the Joint Agency. However, these issues are not directly relevant to the change in question which is simply to require safety data to be submitted and approved at the time of initial application rather than 6 months after approval.

Top of page

Reasons for the change

By evaluating safety data before new products are approved, the TGA will be able to confirm that new excipients are safe before they become available in products for use by consumers. The change is required for the following reasons.

1. Safety

In 22 cases, sponsors of products with new excipients withdrew their product from the ARTG following submission and evaluation of safety data relating to the new excipient. Of these cases, skin irritation had been found in 16, skin sensitisation in 2 and a published article suggesting a link to bladder cancer in a further case. If the data had been evaluated before approval of the product, the products would not have been approved in the absence of further data to establish safety.

In a random sample of 30 evaluated applications, the data showed skin irritation in 30% of cases, skin sensitisation in 6% of cases and eye irritation in 6% of cases. These risks were managed by imposing conditions on the use of the substance in medicines (e.g. an upper concentration limit or a restriction on the route of administration or use in or near the eyes) based on the data.

The TGA's adverse drug reactions database includes many reports of adverse reactions to topical non-prescription medicines. However, it is usually not possible to ascribe a reaction to a particular ingredient in the medicine, particularly if the ingredient causing the problem is an excipient (each product contains a number of excipients).

It is widely acknowledged that voluntary reporting picks up only a small proportion of actual adverse reactions occurring in the community, particularly for non-prescription medicines such as sunscreens where people self-select products without professional intervention. In these circumstances, only the most obvious adverse reactions will be reported and TGA concerns will only be triggered when a sufficient number of reports have been received.

The potential for many adverse reactions can be predicted from standard toxicological tests. For new excipients in medicines other than topical non-prescription medicines, the TGA evaluates these data before approving the excipient for use in products. For excipients in topical non-prescription medicines, under existing arrangements, this evaluation does not take place until at least 6 months after the product is available to consumers.

2. Poor compliance

Under current arrangements sponsors have little incentive to submit data on time or to respond quickly to requests for additional data, despite their provision of written assurances and the imposition of a condition of listing / registration on each product. Following a TGA review in November 2005 it was found that one sponsor had data packages outstanding for 100 products since 2002 and another for over 80 products.

An analysis of submitted data packages showed that around 30% did not include the basic data specified in TGA guidelines. Of the data packages on hand in December 2005, 25 requests for additional data had been outstanding for more than 6 months.

These delays in finalisation of review of data packages expose the agency, and the industry, to criticism if there are adverse reactions to a product containing a new excipient and this could have been predicted from evaluation of the required safety studies before the product was made available to consumers.

3. Lack of certainty for industry and consumers

New excipients, by definition, have not previously been used in medicines in Australia. Under current arrangements there is a 6 month period where the product can legally be supplied without the ingredient having been assessed by the TGA for safety. This creates uncertainty for consumers and for sponsors who may have their product removed from the ARTG if the data are not provided or are unsatisfactory.

The submission of poor quality data (see 'Poor compliance' above) may necessitate ongoing dialogue with the sponsor or their agent and may prolong the 6 month period of uncertainty for consumers and sponsors before a final decision is made.

Some sponsors have chosen to launch a sunscreen with a new excipient then withdraw it before the 6 month period has expired or when they have been challenged to provide the data.

The required assurances do provide some indication of the safety of the ingredient but this is very limited. The ICID reference simply allocates a name to the substance; the fact that the substance is not on the EC negative list for ingredients in cosmetics does not mean that it is safe and the fact that there have been sales of comparable products in other countries for 2 years does not mean there have not been any adverse reactions in those countries.

The majority of the new excipients in non-prescription topical products are in sunscreens. Because of our harsh climate many Australians use sunscreens over large areas of their body for long periods of time. Australians are therefore potentially exposed to larger amounts of product over longer periods of time than may be the case in other countries like Europe or the US. In addition, Australia has the highest rate of skin cancer in the world and the use of sunscreens is a major component of public health messages relating to the prevention of skin cancer. For these reasons it is particularly important to maintain consumer confidence in the safety of sunscreen products.

4. Identification of ingredients

Under existing arrangements sponsors are required to provide an assurance that the ingredient is named in the International Cosmetic Ingredient Dictionary (ICID). However, entries in the ICID are often insufficient to adequately identify the ingredient concerned, especially for biological and herbal ingredients. This can potentially lead to substitution of ingredients (all of which meet the definition of the ICID), which may have safety implications.

5. Lack of equity for some sponsors

Different sponsors may apply to use the same excipient during the 6 month period before the excipient is approved for general use. This can result in a number of sponsors having to submit a data package and pay an evaluation fee of $5270.00 for the same substance. Those sponsors submitting poor quality data gain a 'free-ride' from those that submit better quality data.

Top of page

Objective of regulation

The objective of regulation of medicines is to ensure that consumers have access in a timely manner to medicines that are of good quality, safe and effective. As part of achieving this objective all 'new' ingredients, including those in topical non-prescription medicines, are evaluated to ensure that they are safe for use in medicines.

New excipients in topical medicines are the only group of ingredients that are not evaluated before being released to the community. All active ingredients and all excipients in medicines other than topical medicines must be evaluated before they are approved and marketed. For topical medicines containing new excipients, under existing arrangements the TGA is not able to confirm their safety until the sponsor has submitted the required data for evaluation.

The current arrangements do facilitate consumer access to new topical medicines in a timely manner but do not allow the TGA to confirm that topical medicines including new excipients are safe before they are made available to consumers.

Costs and benefits

There will be no change to existing TGA fees as a result of this change in policy. There will be opportunity costs for industry during the period in which the TGA is evaluating the data (estimated at 28 working days for a new application). There will be potential savings for industry where excipients are found to be unacceptable before being marketed in products - i.e. by avoiding the cost of product cancellation and withdrawal from the market.

The benefits of the change will be:

  • Increased community confidence in the safety of medicines;
  • Greater certainty for sponsors that their products will not be withdrawn for safety reasons; and
  • Better identification of ingredients in products.

Implications for the Joint Agency

There is no equivalent process for new excipients in topical medicines in New Zealand. Sunscreens are not currently regulated as medicines in New Zealand but it is anticipated that they will be regulated as medicines in the Joint Agency.

Stakeholders will be consulted on Joint Agency guidelines for the regulation of new excipients in topical medicines, including sunscreens, as part of the regulatory package to be released for consultation prior to the commencement of the Joint Agency.

Enquiries

For all enquiries contact Dr Ian Copeland, OTC Medicines Section, tel 02 6232 8022, email OTC.Medicines@tga.gov.au.

Top of page

Questions and answers

When does the new policy come into force?

The new policy comes into force on 1 September 2006. From this date, sponsors of topical non-prescription products will be required to provide toxicological data to support the safety of new excipients before the product is listed or registered, rather than within 6 months after listing or registration.

What information is required?

The following information is required in relation to new excipients:

  1. An assurance that the excipient 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'; and
  2. Acute oral toxicity: LD50 - animal or alternative method; and
  3. Irritation study - skin; animal or alternative method; and
  4. Sensitisation study - skin; animal or alternative method.

The following additional studies may be requested in individual cases where concerns become evident at the time of evaluation.

  1. Eye irritation study; and
  2. In vitro mutagenicity (Ames) test; and
  3. In vitro percutaneous absorption test.
  4. Proposal form and attachments for approved name, if required (see below).

This information should be submitted together with the New substance application form (available for use online through the TGA eBusiness Services OPAL system1) and a proposal form for approval of an 'Australian Approved Name' (AAN)3.

If the substance is approved it will be entered (by AAN) in the ELF and OPAL systems and will thereafter be able to be used in other topical non-prescription medicines (subject to any conditions or limitations) without the need for further evaluation. The sponsor will be advised of the AAN when it has been approved.

For new excipients to be included in registered products, the information can be submitted as part of a 'new product application' and evaluated as a single package.

Alternative sources of data on the safety of the excipient will be considered. For instance, if the excipient has been cleared 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 on the Internet4. Copies of NICNAS reviews may be available from the supplier of the excipient.

Fees will apply to the evaluation of the information package as specified in the Summary of fees and charges5.

How long will it take?

The target time for a decision on the safety of a new excipient is 28 working days from the time of receipt in the OTC Section. This does not include any time the sponsor takes to respond to queries.

How do I submit an application for a new excipient?

Applications can be lodged online through the TGA eBusiness Services OPAL system6. For online applications, the information package (including an AAN Approval form8) still needs to be submitted in hard copy to the TGA.

How will the TGA's electronic systems handle the change?

Currently, new excipient ingredients for use in topical products can be made available for selection in ELF once a provisional Australian approved name (known as a 'PRV') has been assigned and appropriate assurances have been provided. However, from 1 September 2006, new excipient ingredients will only be made available for selection in ELF once an Australian approved name (AAN) has been assigned and the safety of the ingredient has been assessed as acceptable.

The only 'PRV' ingredients that will remain on the ARTG beyond 1 September 2006 will be those that are already in products on the ARTG that have not yet been cleared. These will not be available for selection in ELF. As the data packages are evaluated, the PRVs will be changed to AANs or the products cancelled from the ARTG and the PRV removed from the system. In this way the remaining PRV ingredients will be cleared and there should be no more on the ARTG by mid-2007.

Footnotes
  1. www.ebs.tga.gov.au
  2. http://www.tga.gov.au/pdf/forms/medicines-forms-aan-adn-prv.pdf
  3. www.cir-safety.org
  4. www.tga.gov.au/about/fees.htm
  5. www.ebs.tga.gov.au
  6. http://www.tga.gov.au/pdf/forms/medicines-forms-aan-adn-prv.pdf

Top of page

Attachment 1

Current provisions for new excipients9

New excipients in sunscreens

Where a sunscreen contains an excipient ingredient which is not in any product currently included in the Australian Register of Therapeutic Goods (ARTG) for supply in Australia, the excipient must be cleared for use by the TGA.

The following information is required:

  1. Identification of the excipient as a substance included in the CTFA International Cosmetic Ingredient Dictionary (the page number and reference should be quoted); and
  2. 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; and
  3. Assurance that the excipient has been approved by the appropriate regulatory agency in Sweden, Canada, USA, UK or The Netherlands; or (less desirably)
  4. Assurance by the applicant that there have been market-place sales of comparable products containing the excipient in one of those five countries for at least two years; and
  5. Acute oral toxicity: LD50 - animal or alternative method; and
  6. Irritation study - skin; animal or alternative method; and
  7. Sensitisation study - skin; animal or alternative method.

The following additional studies may be requested in individual cases where concerns become evident at the time of evaluation.

  1. Eye irritation study; and
  2. In vitro mutagenicity (Ames) test; and
  3. In vitro percutaneous absorption test.

All of the above information can be submitted prior to listing together with the New substance application form. If the substance is cleared it will be given an 'Australian Approved Name' (AAN) and will thereafter be able to be used in other topical non-prescription medicines (subject to any conditions or limitations) without the need for further evaluation. The sponsor will be advised of the AAN and will then be able to submit an application to list/register the sunscreen product.

Alternative sources of data on the safety of the excipient will be considered. For instance, if the excipient has been cleared 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 on the Internet11. Copies of NICNAS reviews may be available from the supplier of the excipient.

Alternatively, the information in the first four points above can be submitted as part of a 'Listing' application for a sunscreen together with an assurance that the data specified in points 5 to 7 will be provided to the TGA within 6 months of the date of listing of the product. The new excipient will be given a 'provisional AAN' (known as a 'PRV') and the product listed with a condition that the data must be provided within 6 months of listing. Failure to submit the specified data within this time may result in cancellation of the product from the ARTG and recall.

The data will be evaluated by the TGA and, if cleared, the excipient will be given an AAN and will thereafter be able to be used in other topical non-prescription medicines (subject to any conditions or limitations) without the need for further evaluation. If there are concerns about the safety of the excipient or if the data provided by the sponsor are incomplete or otherwise unacceptable, the product may be cancelled from the register and/or recalled.

Fees will apply to the evaluation of the data and the listing of the product as specified in the Summary of fees and charges.

Footnotes
  1. From Australian Regulatory Guidelines for OTC Medicines (ARGOM), Chapter 10)
  2. www.cir-safety.org

Top of page