ADEC process and Product Information documents

It is in the interests of both the TGA and industry that the approval of product information and finalisation of other matters in the post-ADEC period proceed as smoothly and efficiently as possible. However, in recent years this process seems to have been subject to delays, partly arising from confusion over when it is best to negotiate on an Australian product Prescribing Information (PI) and Consumer Medicine Information (CMI) document.

In the pre-ADEC period, the sponsor will have been sent an overview with a covering letter requesting certain changes be made to the PI. Prior to this, companies will also have received edited copies of their major evaluation reports with recommendations for changes to the PI. As part of the pre-ADEC response, companies are requested to provide an updated copy of the PI. It is in the interests of companies to consider doing this at this point in time. An updated PI, even if not accepted as being in final form subsequently, will speed up future negotiations in the post-ADEC period should the application be successful.

In general, the PI prepared for consideration by the ADEC and the Delegate at this point in time should include the revisions requested by the evaluators and the Delegate, or commentary as to why recommendations for alterations have not been made.

In the week following ADEC, the companies receive a copy of the ADEC resolution that will indicate if the application is recommended for approval or not. They will usually be contacted shortly thereafter by the clinical Delegates who will request revisions to the PI. Speedy resolution of issues associated with the PI will lead to faster approval times. If companies feel that requests by the TGA in relation to the PI are not reasonable, it is requested that they contact the Delegate directly to discuss this matter and also provide a justification as to why changes should not be implemented.

The TGA appreciates that for many companies final approval for text to the PI must be obtained from Head Office. Nevertheless, with judicious use of electronic communications this should not necessarily be a barrier to a rapid clearance of the PI. In preparing documents in general, companies should note that both the ADEC and the TGA take note of internationally-repared documents, for example those that have been approved for use in the European Union or the United States of America, if relevant. Omission of significant warnings, precautions or other information contained in these documents and included in the dossier in Australia, is likely to lead to requests for the information to be included. Companies should also be aware that the ADEC and the Delegates do favour tabular presentation of material in the clinical trials section accompanied by explanatory text.

CMI should be submitted at the same time as the PI in the post-ADEC period. It is easiest for the Delegate and other staff to evaluate a CMI against the requirements of the legislation at the point of time that the PI is being finalised.

In the same post-ADEC period, companies may be asked to confirm details relating to register entries, including provisional ARTG entries. While these will have, in principle, been cleared by companies in the period before the ADEC and before the Part II pharmaceutical chemistry or laboratory evaluation is complete, it is the experience of the TGA that companies may later wish to make corrections. It is critical that these documents be reviewed speedily and that the information, including justification for corrections, be provided to the TGA if there are any changes to be requested in the early post-ADEC period. It is also critical that if a product has reached the post-ADEC phase without full GMP clearance, that the matter be finalised as soon as possible. Finalisation can only occur with the provision of adequate evidence of GMP certification. Companies are advised that the post-ADEC period is not the preferred time for GMP matters to be dealt with. This should be dealt with as part of the evaluation process. It is not possible for the TGA delegates to approve products that do not have acceptable GMP.

Under the proposed Premier system, all matters relating to product PAR and GMP clearances must be finalised pre-ADEC.

In summary, in order to speed up the approval process post-ADEC for prescription medical products, it is in a company's best interests to ensure that outstanding evaluation matters such as GMP certification are cleared, that the product information has been updated as far as possible to meet the requirements of Delegates and to a standard similar to that used internationally, and that the provisional ARTG record details have been fully checked. The TGA can then most efficiently finalise applications and issue certificates of registration.

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Analgesics review

In March 2002, the Medicines Evaluation Committee considered publicity around a published report of a small number of Australian cases of adverse reactions to analgesics. The committee had considered safety and overdose issues with paracetamol on a number of occasions in the past and the labelling of paracetamol had been thoroughly reviewed. Nevertheless, the committee recommended that further data be sought to determine the current extent of the problem in Australia with respect to the incidence of liver toxicity and the frequency of liver transplants following paracetamol overdose, particularly when used in high doses and for prolonged periods as well as in acute overdose. This review commenced in July 2002 and the committee is scheduled to consider the report at its meeting on 7 November 2002 and make recommendations to the TGA following that meeting.

Application forms for advertising approval

The Advertising Unit of the TGA, in conjunction with the Advertising Services Managers of the Australian Self Medication Industry (ASMI) and the Complementary Healthcare Council of Australia (CHC), have developed draft advertising approval application forms for specified and broadcast media.

The purpose of these forms is to simplify the application for advertisers, streamline the approval process, improve customer service and reduce processing times by standardising the type of information needed to approve an advertisement for consumer medicines appearing in specified and broadcast media.

The forms are being trialed for five months from 1 July 2002 until 29 November 2002. At the end of this trial period, all comments will be collated and taken into consideration before a final version is released.

The TGA and the Advertising Services Managers expect that these forms will become the standard for submitting applications and encourage advertisers to trial them and provide comments to make sure the forms achieve the result we are hoping for.

Please send your comments and feedback to the Advertising Unit at:

Mail: Advertising Unit, TGA, PO Box 100, WODEN ACT 2602
Fax: 02 6232 8659
Email: tga.advertising@tga.gov.au

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Concern over "homoeopathic meningococcal vaccine"

With the recent community concerns around the prevention of meningococcal disease, evidence has emerged that a product, presented as a "homoeopathic meningococcal vaccine", may be being offered in Australia. The Therapeutic Goods Administration considers that the promotion or use of such a product as a preventative measure against meningococcal disease is entirely inappropriate. Use of products of this type may be hazardous. Patients who are treated with these products, believing they are effective in preventing infection, may be placed at serious risk.

According to the National Health and Medical Research Council's The Australian Immunisation Handbook*, homoeopathic "immunisation" is not considered to be proven to give protection against infectious diseases; only conventional immunisation provides a measurable immune response. Further, the Handbook quotes a statement issued in 1993 by the Council of the Faculty of the Homoeopathy, London, strongly supporting conventional vaccination and has stated that vaccination should be carried out in the normal way, using the conventional tested and proved vaccines, in the absence of medical contraindications. The Executive Director of the Australian Natural Therapies Association is also quoted as stating that no properly qualified natural therapist would recommend homoeopathic "immunisation" as an alternative to conventional immunisation.

Under therapeutic goods legislation, homoeopathic medicines that meet certain conditions are exempt from some of the normal regulatory requirements that apply to other medicines. However, homoeopathic products which claim or suggest that they can treat serious disease, such as meningococcal infection, would not be exempt from normal regulatory requirements on medicines and would have to be included on the Australian Register of Therapeutic Goods (ARTG) as a Listed medicine. Under the advertising legislative provisions, references to serious diseases are not permitted on medicine labels unless a specific exemption has been granted by the TGA after being satisfied the medicine is safe and effective. There are no such products included on the ARTG and it unlikely that a "homoeopathic vaccine" would be granted an exemption by the TGA.

The TGA is very concerned that there may be other homoeopathic "immunisation" products being offered in Australia as an alternative to conventional immunisation and is currently working with the States and Territories and other stakeholders to prevent further promotion or use of these products.

* National Health and Medical Research Council (2000), The Australian Immunisation Handbook, Department of Health and Family Services, Canberra.

European Union guidelines

Since July 2002, four more European Union Guidelines have been published as adopted in Australia.

EU Guidelines are generated by the Committee for Proprietary Medicinal Products (CPMP) and International Conference on Harmonisation (ICH) and are to be regarded as part of Volume 1 of the Australian Guidelines for the Registration of Drugs (AGRD).

• EU guidelines published as adopted in Australia <http://www.tga.gov.au/docs/html/euguidad.htm>
• EU guidelines published as NOT adopted in Australia <http://www.tga.gov.au/docs/html/euguidenotad.htm>
• EU guidelines replaced or superseded <http://www.tga.gov.au/docs/html/euguidsup.htm>

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Hormone replacement therapy

Many people will be aware of the recent controversy concerning use of hormone replacement therapy (HRT) in women. In response to the early publication of an article raising concerns about HRT, an Expert Advisory Committee was convened within 24 hours. The Committee was requested to analyse the published article and provide advice on its significance in the Australian setting. The report of this Committee was available within days and is published on this website.

• Report of Expert Committee convened by the Therapeutic Goods Administration to assess the findings of a report on the safety of the US Women's Health Initiative (combined Hormone Replacement Therapy) trial <http://www.tga.gov.au/docs/html/hrtreport.htm>

New substances approved for listed medicines

On 24 July 2002, emu oil was gazetted <http://www.tga.gov.au/legis/tgnlist0205.htm> as an approved substance for use as an active ingredient in listable therapeutic goods. On 16 October 2002 the following substances were gazetted for use in listable therapeutic goods: boric acid, borax, sodium perborate and borax pentahydrate; molybdenum trioxide; and magnesium phosphate dibasic trihydrate <http://www.tga.gov.au/legis/tgnlist0206.htm>.

Restricted substances information seminar and launch of TGA training package

Terry Slater, TGA National Manager,
opens the TGA information seminar

Representatives from over forty companies recently attended a TGA information seminar aimed at clarifying certain aspects of the responsibilities and requirements for importing and exporting restricted substances under Customs legislation and distribution of controlled drugs under Schedule 8 of the Standard for the Uniform Scheduling of Drugs and Poisons. The TGA's National Manager, Terry Slater, opened the seminar with the launch of a TGA training package which will assist industry to educate their employees in the control and monitoring of drugs and chemicals to prevent their diversion for illicit use.

Mr Slater spoke of the rising concerns about chemical diversion from legitimate uses into illicit products, and the increasing demands on those members of the licit industry to take appropriate action against this, without the need to impose further regulatory controls.

The keynote speakers at the seminar were:

• Ms Sue Kerr (Head, Drug Strategy and Health Promotion Branch, Population Health Division, Commonwealth Department of Health and Ageing)
• Mr Martin Davies (Australian Customs Service)
• Detective Inspector Paul Willingham (NSW Crime Agencies)
• Ms Sharyn McGregor, Ms Cheryl Regan and Dr Michael Pitt (Treaties and Export Section, TGA).

Detective Inspector Paul Willingham also emphasised the need for a cooperative approach to the prevention of chemical diversion across law enforcement, regulators, and the chemical and pharmaceutical industries.

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Safety Recall - Kava-containing medicines

In August 2002, the Therapeutic Goods Administration initiated a voluntary recall of kava-containing medicines included on the Australian Register of Therapeutic Goods (ARTG). Prior to the recall, the TGA had been closely monitoring the situation in Australia and internationally following overseas reports about concerns of liver damage associated with the use of kava-containing medicines.

As part of its strategy for managing the on-going safety of these medicines, the TGA, in January 2002, wrote to sponsors of kava-containing medicines requesting them to remain vigilant to reports of possible adverse reactions. At the same time, the TGA issued alerts to Australian consumers and health professionals about the potential safety concerns associated with the use of these medicines. The TGA continued to monitor both the Australian and international situation for adverse reactions associated with kava-containing medicines.

Until recently, there was no indication that kava-containing medicines in Australia presented a risk. However, in July 2002, the TGA become aware of the death from complications of liver failure of a woman in Australia who had been taking, among other complementary medicines, a kava-containing medicine. After considering advice from the Adverse Drug Reactions Advisory Committee and the Complementary Medicines Evaluation Committee regarding the safety of kava-containing medicines, the TGA decided that it was unable to exclude the possibility that these medicines may cause serious liver damage. Consequently, as a precaution, the TGA initiated a voluntary recall to consumer level of all medicines containing kava included on the ARTG. Prior to taking this action, the TGA consulted with the complementary medicines industry over its concerns and the need for a recall.

The TGA has also written to all sponsors of kava-containing medicines included on the ARTG advising them that they have twenty-eight days to provide the TGA with evidence that their product is safe. At the end of this time, the TGA will evaluate the evidence and make a decision as to the suitability of kava-containing medicines remaining on the Australian market as Listed medicines.

Internationally, concerns over the health risk associated with the use of kava-containing medicines have prompted regulatory agencies in other countries, including Germany, Singapore, Switzerland, France, Ireland, Portugal, Austria, the United Kingdom, the United States of America and Canada, to take actions ranging from warning consumers about potential risks, to removing kava-containing medicines from the marketplace.

In reaching a regulatory decision in this matter, the TGA will take into account the actions taken elsewhere, the results of consultation with experts in the area of medicines safety and kava production, and the advice from its expert Committees.

TGA policy for the export of medicines and operational guidelines

As part of the implementation of the recommendations arising from the Review of the Regulatory Regime for the Export of Therapeutic Goods, 1997, the TGA committed itself to the development of a clear and transparent export policy for medicines. Following an extensive period of consultation with the peak industry associations, this policy document has been finalised and is now available.

• Therapeutic Goods Administration (TGA) Policy for the Export of Medicines from Australia <http://www.tga.gov.au/docs/html/export/exppol.htm>

Operational guidelines, which supplement the policy document, have also been developed and are available.

• Exporting Medicines from Australia - Operational Guidelines <http://www.tga.gov.au/docs/html/export/expopgui.htm>

Sponsors of medicines for export are encouraged to use these documents for reference purposes to ensure the efficient processing of listing of export medicines and related certificates of pharmaceutical products.