European Union (EU) guidelines

Since October 2001, over seventy new and replacement European Guidelines <http://www.tga.gov.au/docs/html/euguideh.htm> have been adopted in Australia.

Dissolution of folic acid tablets

A survey of 51 nutritional supplement products containing folic acid has been completed by TGA Laboratories. The survey examined compliance of the products with the dissolution requirements of the United States Pharmacopoeia and included tablets containing 100 micrograms or more of folic acid available in Australia. The survey was undertaken in response to the findings that poor dissolution rates had been observed for a number of products available in the United States. Concerns were raised that poor dissolution may have direct consequences for the bioavailability of the folic acid, especially in those situations where it is indicated or used for the prevention of neural tube defects.

TGAL found that 10 of the 51 products failed to meet USP dissolution standards for release of folic acid. Several products also failed to comply with the disintegration standard that is the legal requirement for this type of product. There is currently no official requirement for folic acid supplements to comply with dissolution standards but given the possibility that poor dissolution may be associated with reduced bioavailability and therefore product efficacy, the test results are of some concern.

Following advice from the Complementary Medicines Evaluation Committee, TGA has sought comment from sponsors and manufacturers on the introduction of a mandatory dissolution standard for tablets containing 100 micrograms or more of folic acid. Details of the proposal can be viewed on the TGA web site.

Medicine labelling notes

Labelling of preservatives in inhalation solutions

The Drug Safety and Evaluation Branch has had enquiries about the required labelling of preservatives in inhalation solutions in Australia. The current General Requirements for Labels for Medicines (Therapeutic Goods Order No. 69), applicable to new registered products, requires that the labels of preparations for use on skin or mucous membranes include the name of any antimicrobial preservative in the goods.

Preservatives are included in some multi-dose inhalation solutions intended for delivery to the lungs or nose, which are mucous tissues. Thus sponsors are reminded that the presence of agents such as benzalkonium chloride, which has been implicated in causing bronchoconstriction in some patients with hyperactive airways, must be disclosed on the labelling of any new inhalation solutions under TGO No. 69. While the new labelling Order is not mandatory until July 2004 for existing products, sponsors of multi-dose inhalation solutions should check their product labels and take steps at the next label print run to comply if necessary.

Edetic acid and its salts (especially disodium edetate) can be considered as preservatives and sponsors are strongly encouraged to disclose the presence of these agents in the labels of their inhalation products as well.

Under current Drug Safety and Evaluation Branch policy, applications or notifications for changes which concern only the adoption of a new or updated official standard are not charged a fee by the TGA.

Labelling of enteric-coated products

The method of administration of enteric-coated medicines can affect the coating, which can be important for safety or efficacy. Labelling of medicines under both the new TGO No. 69 and the previous TGO No. 48 require inclusion of the 'name of the dosage form'. For enteric-coated products, this should be an appropriate phrase, e.g. 'enteric-coated tablets'. Sponsors of such products should take steps to ensure that their products are appropriately labelled. If revision is required, a category 3 application should be submitted.

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ELF3 update

Work on the online Electronic Listing Facility version 3 (ELF3) is continuing to progress. The TGA has recently focused its effort towards writing the ELF3 business rules. This work has been largely completed and the TGA is now focusing on preparing scenarios to be used to test the functioning of the system and the correctness of the business rules when formal TGA User Acceptance Testing (UAT) commences. Because of the complexity of the system and the business rules, a large number of test scenarios are needed to effectively put the new system through the hoops. The assistance of the complementary medicine industry peak bodies, by providing example test scenarios, has been sought.

Retirement of ADRAC Chair

The 14 December 2001 meeting of the Adverse Drug Reactions Advisory Committee (ADRAC) saw the retirement of Associate Professor Timothy Mathew as Chair of the Committee. Members conveyed their gratitude for Dr Mathew for his dedication and professionalism during 16 years of service to the Committee. Dr Mathew joined ADRAC as a member in February 1985 and has been Chair since July 1993.

Dr Mathew has made a very great contribution to ADRAC. He has provided invaluable expertise in the area of renal medicine but also has contributed a comprehensive understanding of drug safety and the role of ADRAC. He has particularly sought to have a appropriate relationship between the Australian pharmaceutical industry and the Committee based on cooperation and mutual respect for respective professional abilities. During his Chairmanship, the stature and responsibility of the Committee has increased The number of Australian reports received has risen from about 7,000 annually to over 12,000 annually during this time. The Australian Adverse Drug Reactions Bulletin has been published regularly and continues to be widely read and highly regarded. Dr Mathew has encouraged the wider publication of information from ADRAC reports and co-authoured three papers in conjunction with secretariat staff. He has also created opportunities for trainee physicians in clinical pharmacology to attend meetings of ADRAC.

The Commitee's role in the assessment of the safety of medicines has extended to include OTC and complementary medicines and, more recently, the monitoring of the safety of vaccines has been intensified. One of Dr Mathew's great strengths has been his ability to lead the Committee through the many important issues which ADRAC addressed. Despite the high volume of material to be considered, under Dr Mathew's direction the Committee has always given adequate consideration to the issues at each meeting. Dr Mathew has also been a core member of ADEC for 9 years and has provided an invaluable link between the two committees.

In parallel with his contributions to ADEC and ADRAC , Dr Mathew has been Chair of the Board of the Australian and New Zealand Dialysis and Transplant Registry since 1977, is National President of the Australian Kidney Foundation and Chair, Therapeutics Committee, Royal Australasian College of Physicians.

Dr Mathew's successor as Chair of ADRAC is Associate Professor Duncan Topliss, Director, Department of Endocrinology and Diabetes at the Alfred Hospital, Melbourne.

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Data requirements for new sunscreen active ingredients

The Medicines Evaluation Committee (MEC) advises the TGA on the regulation of OTC medicines (including sunscreens) in Australia. The committee recently considered data requirements to support the approval of new sunscreening agents for use in listed sunscreen products.

For the benefit of sponsors who may be considering a new sunscreening agent, the committee's initial advice is available on our website. This advice is of a general nature and is intended to assist sponsors in submitting appropriate data. A different approach may be warranted for particular substances.

New substances approved for listed medicines

Since the last update, provided in the October 2001 edition of TGA News, the following new substances have been approved for use as active ingredients in listed medicines:

• Demineralised fish proteoglycan extract
• Black boned chicken powder
• Conifer phytosterol complex

Compositional guidelines are available for each of the above substances and may be obtained by contacting the Office of Complementary Medicines. Compositional guidelines are formulated where no pharmacopoeial monograph exists. They are intended to compositionally define new substances permitted for use in listed medicines and to limit parameters that may affect the safety of the substance.

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"Practitioner Only" listed medicines

While it is recognised that some Listed medicines may be exclusively supplied through complementary healthcare practitioners, sponsors should be aware that these 'practitioner only' goods must be Listed or Registered in the Australian Register of Therapeutic Goods (ARTG). Listed products that are supplied only to practitioners must comply with the same standards and requirements that apply to all Listed medicines. The only special provision for 'practitioner only' goods relates to some labelling requirements (refer Therapeutic Goods Order No. 69 "General requirements for labels for medicines").

Sponsors should note that the supply of a medicine to a practitioner without Listing or Registering that good in the ARTG constitutes illegal supply. Practitioners should also be aware that in some instances, the medicines that they supply to their patients are required to be Listed or Registered in the ARTG. For example, the preparation of a herbal medicine by a practitioner for an individual patient at the time of consultation is exempt from the Act. However, if the practitioner imports a herbal medicine to supply to their patients, then the practitioner is legally the sponsor and the medicine is required to be in the ARTG before supply.

There are provisions in the Act that allow for the importation and use of unapproved medicines under certain circumstances and information on these can be found on the TGA web site under the heading "Unapproved Medicines".

Recent ADEC membership appointments

Following consultation with the expert medical Colleges and Societies, Associate Professor Andrew Dawson, Dr Kate Stern and Associate Professor John Tapsall were recently appointed to associate membership of the Australian Drug Evaluation Committee (ADEC) by (then) Minister for Health, Dr Wooldridge. Associate Professor Dawson is a specialist in clinical pharmacology and toxicology at the Newcastle Mater Hospital. Dr Stern, of the Royal Women's Hospital, Melbourne, specialises in obstetrics and gynaecology. Associate Professor Tapsall is a specialist in clinical microbiology and infectious diseases, based at the Prince of Wales Hospital, Randwick.

The appointments were made to replace ADEC members whose terms of office were due to expire or who were retiring from the committee due to other commitments. The TGA expresses gratitude for the service given to the committee and the advice provided to the Minister and Secretary by the outgoing members: Dr Rosemary Ayton, Dr Keryn Christiansen, Associate Professor Tim Mathew and Associate Professor Anne Tonkin. Dr Ayton served on the ADEC for 10 years, as a core member for the past 5 years. Dr Christiansen served for 3 years as a core member; Associate Professor Mathew served 9 years as a core member; and Associate Professor Tonkin served almost 5 years as a core member.

The Minister has appointed to the core membership of the ADEC, Professor Leonard Arnolda, Dr Alyson Kakakios and Dr Anne Mijch; all of whom were previously associate members. Core members attend all meetings of the committee while associate members attend whenever medicines in their areas of expertise are to be considered by the ADEC, as determined by the chairman. ADEC decisions are made on a collegiate basis.

The function of the ADEC is to make medical and scientific evaluations of prescription medicines, and advise on other matters, as requested by the Minister or Secretary. Associate members are appointed for 5-year terms, while core members are appointed for 3-year terms. The Minister may re-appoint a member at the conclusion of their term.

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Retirement of Susan Walters

Dr Susan Walters, the Head of the Pharmaceutical Chemistry Evaluation Section of the Drug Safety and Evaluation Branch retired in October 2001 after a long career in the TGA and its precursor organisations. Susan joined the National Biological Standards Laboratory (NBSL), then part of the Department of Health, in the early 1970s after completing her Ph.D. in the UK and a period of employment with a major pharmaceutical company in Sydney. She carried on her work on dissolution testing in NBSL and subsequently developed a long term interest in the effect of dissolution on the bioavailability of solid oral dosage forms.

Following a reorganisation of the Pharmaceutical Chemistry Section of NBSL in the mid 1980s, Susan took over as the leader of a group assigned the task of evaluating the chemistry, quality control and bioavailability components of applications to market prescription only medicines, a role she continued with until her retirement. The changes in the intervening years were many and profound and included her promotion to the Pharmaceutical Chemistry Evaluation Section Head position in the Drug Evaluation Branch, to the introduction of the Therapeutic Goods Act and the adoption of the EU Guidelines following the Baume report on Drug Evaluation in Australia.

Over the years Susan was instrumental in the development of many policies and standard operating procedures aimed at ensuring the efficient and comprehensive evaluation of the Part II and bioavailability components of applications to register prescription only medicines, taking into account contemporary advances in pharmaceutical science and technology. She liaised closely with the pharmaceutical industry through relevant industry groups and the Association of Regulatory and Clinical Scientists, to ensure the understanding of the numerous guidelines and Appendices of the AGRD. Susan also maintained close liaison with other national drug regulatory authorities such as the New Zealand Medsafe, the UK's MCA, the USFDA and others. She has provided training to evaluators from the newer national regulatory authorities of Indonesia and Singapore. Susan also worked with the World Health Organization (WHO) and was a key figure in the 1998 WHO publication on multisource (generic) products: "A Manual for Drug Regulatory Authorities"

Susan is not retiring from work, but plans an active role in teaching students of drug evaluation and continuation of her involvement in retail pharmacy.

Aristolochic acid testing program

Over the last couple of years, TGA Laboratories has been actively involved in the analysis of herbal medicines for the presence of aristolochic acid, a substance strongly associated with renal failures and cancer. Where aristolochic acid has been detected, the TGA has acted on the laboratory's findings by recalling affected batches and, in some cases, cancelling products from the ARTG. As well, TGA has moved to prohibit the use of herbs known to contain aristolochic acid. Furthermore, TGA now requires sponsors to ensure that any herb that may be inadvertently confused with one that contains aristolochic acid, or any product that contains such a herb, is tested to confirm the absence of aristolochic acid prior to release for sale in Australia.

Even with these extensive controls in place, samples containing aristolochic acid continue to be detected by TGAL. In the latest episode, three products have tested positive for aristolochic acid despite there being no indication from the declared ingredients that aristolochic acid could be present. The samples were tested as part of a survey of products that bear the names of certain Traditional Chinese Medicines. The products chosen for testing were ones where the formula of the patent medicine given in the Chinese Pharmacopoeia indicated that it was at risk of containing aristolochic acid, but where the 'suspect' ingredient in the formula was not included on the product label or in the formulation details held by the ARTG. Regulatory action is being taken in relation to these products.