Australian Drug Evaluation Committee news

New members appointed to ADEC

New appointments to the Australian Drug Evaluation Committee were announced in May. Dr Keryn Christiansen a clinical microbiologist from Perth has been appointed to core membership for a three year term. Six other new Associate Members were appointed to vacancies on the committee.

Associate Professor Leonard Arnolda
Cardiologist, Adelaide

Professor Ross StC Barnetson
Dermatologist, Sydney

Associate Professor David Le Couteur
Clinical Pharmacologist and Geriatric Medicine, Canberra

Dr Anne Mijch
Clinical Microbiologist and Infectious Diseases, Melbourne

Associate Professor Ian Power
Anaesthesia and Pain Management, Sydney

Professor John Marley
General Practice, Adelaide and

Dr George Skowronski
Intensive Care, Sydney

Core Members are appointed for a three year term and Associate Members a five year term. The Committee is chaired by Sydney oncologist, Professor Martin Tattersall.

Ratification and release of ADEC minutes between meetings

The early release of ADEC Minutes has been sought by industry for many years. Successive reports by Baume in 1991 and Hayes in 1996 have reinforced the need for minutes to be available promptly following meetings. The minutes are required to be a detailed record allowing ready understanding of how decisions were reached. Since last October, ADEC has been trialing an Internet on-line discussion forum to allow ratification of minutes to occur between meetings and facilitate early release. Unfortunately technology problems have hampered this objective and the trials to date have only achieved partial success. As an interim measure at its 196th Meeting the Committee agreed to allow early release of unratified final draft Minutes to Sponsors on request. Unratified final draft minutes have been approved by key speakers and by the Chairman but have not been cleared by all members present at the meeting. If changes are made at the time of ratification sponsors are provided with the revised minutes. Sponsors seeking early release of ADEC minutes should contact the Secretary (Tel. (02) 6232 8250). It is hoped that Sponsors will confine requests for early release of unratified final draft Minutes to those where there are pressing circumstances. The Secretariat is working to overcome the technical difficulties encountered so far.

Revision of ADEC Medicines in Pregnancy Handbook 3rd edition

At the request of the Australian Drug Evaluation Committee a group comprising of the following people is revising the Medicines in Pregnancy Handbook. <http://www.tga.gov.au/docs/html/medpreg.htm>

Dr Rosemary Ayton Chairman,
Gynaecologist/Obstetrician

A/Professor William Webster
Teratologist

Dr Christine Tippett
Obstetrician

Dr Paul Lancaster
Perinatal Statistics & Research

Dr Eric Haan
Geneticist

Dr Timothy Mathew
Nephrologist, Chairman of ADRAC

Mr Ron Batagol
Pharmacy & Drug Information Consultant; Pharmacist with special interest in the effects of drugs on pregnancy

Dr Pat Purcell
Medical Officer, Acting Secretary of ADRAC, TGA

Dr John Donohoe
Toxicologist, Drug Toxicology Evaluation Section, TGA

Dr Nena Waight-Sharma
Secretary of Working Party, TGA

Work has commenced to check the categorisation of drugs approved in Australia since the last edition and examine any discrepancies or changes that have arisen. Industry groups are invited to submit any comments about the publication and sponsors are welcome to raise any issues pertaining to individual drugs. Publication is anticipated early in 1999.

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Important information for regulatory affairs staff

The Drug safety and evaluation Branch has advised the Australian Pharmaceutical Manufacturers Association of several matters recently:

• Periodic safety update reports
• Pictures on labels
• Product Information for antibiotic products
• Toxicology and clinical study reports - need for signature

Periodic safety update reports

As from 1 August 1998, the wording in approval letters of conditions of registration concerning submission of post marketing reports has been amended to encourage the submission of Periodic Safety Update Reports. The new wording is:

"Post marketing reports are to be provided annually until the period covered by such reports is not less than three years from the date of this approval letter. No fewer than three annual reports are required. The reports are to meet the requirements for Periodic Safety Update Reports as described in ICH document Topic E2 (CPMP/ICH/288/95). Unless agreed separately between the supplier who is the recipient of the approval and the TGA, the first report must be submitted to TGA no later than 15 calendar months after the date of this approval letter. The subsequent reports must be submitted no less frequently than annually from the date of the first submitted report. The annual submission may be made up of two Periodic Safety Update Reports each covering six months. If the sponsor wishes, the six monthly reports may be submitted separately as they become available. Submission of the report must be submitted within the sixty days of the data lock point for the report (or, where applicable, the second of the two six monthly reports), as required by CPMP/ICH/288/95. Each report is to be accompanied by a statement of the amount of each presentation of the product issued in Australia in the same period (or a period to the same)."

The letter will go on to state that where Periodic Safety Update Reports are not available, the sponsor will be required to submit annual reports in the existing Australian format. While the requirements for Periodic Safety Update Reports will not be made retrospective, the TGA will accept Periodic Safety Update Reports in place of annual post marketing reports for products approved before 1 August 1998, should sponsors elect to submit them.

Pictures on labels

It has come to TGA's attention that some sponsors have added pictures or other graphical representations to the labels of products evaluated by DSEB without prior approval. Products evaluated by DSEB are those subject to Schedule 10 of the Regulations under the Therapeutic Goods Act 1989, mainly prescription drugs and injectables. In some cases, sponsors may have added pictures or graphical representations after a draft label without pictures has been approved. It is of concern to TGA that pictures or graphical representations can represent an indication and DSEB reviews such changes to ensure that the approved indications are not being implicitly extended.

Section 17 of the Appendix 8 of the Australian Guidelines for the Registration of Goods Volume 1 (AGRD1) allows only certain changes to labels without prior approval and changes to content are explicitly excluded (17.11). Insertion of a picture of graphical representation constitutes a change to content and therefore requires prior approval, normally by means of a Category 3 application.

Sponsors who have made such changes without prior approval should be aware that they have contravened the conditions of registration and the changes render the labels unapproved. Such changes should be declared to TGA before 1 October 1998 and formal approval sought. Companies complying with this timeframe will incur no formal sanction. After this date, TGA may seek sanctions for breaches of the Therapeutic Goods Act 1989.

Product Information for antibiotic products

For many years, sponsors of antibiotic products have been required to include a Precaution statement about the risk of antibiotic-associated colitis. The great majority of these statements include advice that oral vancomycin should be used to treat this condition. Most commonly, the Precaution includes a sentence stating: "However, in moderate to severe cases appropriate therapy such as oral antibacterial agents effective against C.difficile (eg. vancomycin) should be considered."

In view of current worldwide efforts to limit the use of vancomycin because of increasing development of vancomycin-resistant enterococci and staphylococci, vancomycin is no longer considered the therapy of choice for the treatment of Clostridium difficile-associated colitis. There is, therefore, a need to amend the statements which currently appear in product information documents for antibiotics to read: "However, in moderate to severe cases appropriate therapy with a suitable oral antibacterial agent effective against C.difficile should be considered."

Drug safety and evaluation Branch will process applications for approval of this change without charge provided:

• The application is made using a form titled "Application to Change the Colitis Precaution Statement" .
• The declaration in the form is completed.
• The form is received by TGA no later than 31 December 1998.

Toxicology and clinical study reports - need for signature

The TGA has noted some inconsistency between various guidelines in relation to the need for toxicology and clinical study reports (including bioavailability study reports) to be signed by the principal investigator. Evidence of a principal investigator accepting the responsibility for the conduct of a study is regarded as essential by TGA. For reports of all toxicology and clinical (including bioavailability) studies commenced after 1 August 1998, evidence must be provided that the principal investigator(s) has signed the report, either in an unqualified fashion or clearly taking responsibility for all aspects of the conduct of the study for which the investigator(s) might reasonably be held responsible. If this evidence is not provided, it will be sought by TGA during the evaluation process.