TGA approach to minimising the risk of exposure to Transmissible Spongiform Encephalopathies (TSEs) through medicines and medical devices
Purpose
The TGA approach and Supplementary Guidance document <http://www.tga.gov.au/docs/html/tsesupp.htm> aims to minimise the risk of exposure to TSEs through the use of medicines or medical devices in Australia.
Potential exposure to TSEs
TSEs, caused by agents known as prions, include scrapie in sheep and goats, chronic wasting disease in deer, bovine spongiform encephalopathy (BSE) in cattle, and Kuru, Creutzfeldt-Jacob Disease (CJD) and New Variant CJD (vCJD) in humans. vCJD is believed to be caused by the agent responsible for BSE in cattle. The emergence of BSE in the United Kingdom and its spread to other countries in Europe, Japan and the Middle East, together with the increasing number of cases of vCJD in humans, have focussed international efforts on minimising the potential for this agent to be transmitted to humans. It is generally accepted that BSE may be transmitted from animals to humans by consumption of contaminated food of animal origin.
There is no evidence to date that BSE has been transmitted by the use of products of animal or human origin in medicines (including vaccines) and medical devices. However, transmission of the classical form of CJD has been reported via human pituitary extracts and certain tissues such as dura mater and corneas. While there have been no reported cases of vCJD in Australia, the TGA believes, that in the interests of protecting public health and safety, the potential risks of exposure to these agents in the manufacture and use of medicines and medical devices should be minimised.
This position is consistent with actions being taken by regulatory agencies in many other countries, including the USA, Canada, Japan, United Kingdom and other European countries. These countries have either recommended against or prohibited the use of ruminant animal (particularly cattle, sheep and goats) derived ingredients from countries with reported BSE incidences in the manufacture of medicinal products. The position is also consistent with the precautionary policy recently adopted in Australia and several other countries that prohibits people who have lived in the United Kingdom for more than six months between 1980 and 1996 from donating blood.
TGA approach
To minimise the potential risk of exposure to TSEs, and particularly BSE, the TGA will ensure that medicines and medical devices do not contain material of animal or human origin from countries where there is a known risk of BSE except where such use can be fully justified. The TGA will achieve this by:
- Requiring that all new products submitted to the TGA for inclusion on the Australian Register of Therapeutic Goods contain or use in their manufacture only animal or human products which are sourced from BSE-free countries or, where this is not possible, there is an assessment of the evidence as to the TSE safety of the material used;
- Continuing to review existing medicines and medical devices to identify any potential risks of exposure to TSEs with a view to removing the use of animal or human products sourced from countries with a known risk of BSE, except where such use can be justified. This review will include active and inactive biological ingredients, as well as biological materials used in production processes but which may not be present in significant amounts in the final product.
The TGA has implemented a step-wise risk management approach to the assessment of ruminant materials used in therapeutic goods. This approach has been endorsed by the National Health and Medical Research Council Special Expert Committee on TSE. If a therapeutic good is injectable, implantable, or introduced through the intra-ocular or intra-tracheal routes and it either contains or is manufactured using materials or reagents of ruminant origin, it must be evaluated by the TGA for TSE safety.
The TGA has adopted the European Medicines Agency (EMEA) Note for Guidance on Minimising the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and Veterinary Medicinal Products (EMEA/410/01 rev 2, October 2003 (pdf,181kb) <http://www.emea.europa.eu/pdfs/human/bwp/TSE%20NFG%20410-rev2.pdf>. If any therapeutic good either contains or is manufactured using ruminant materials or reagents classified by the EMEA as Category A or B (high or low risk of TSE infectivity respectively), the product must be fully evaluated by the TGA. For other therapeutic goods (ie. oral and topical presentations), which contain or are manufactured using ruminant materials classified by the EMEA as Category C (no detectable infectivity), a self-assessment is required by the Sponsor or Manufacturer according to the TGA Supplementary requirements for therapeutic goods for minimising the risk of transmitting transmissible spongiform encephalopathies. TGA will include self-assessable products in the ongoing review of all therapeutic goods to ensure that Sponsors and Manufacturers are conducting the self-assessment in accordance with the TGA Supplementary Requirements. A questionnaire has also been created as an aid to Sponsors and Manufacturers to obtain information from suppliers. Insert link to questionnaire here. TGA's requirements for the assessment of medical devices containing animal materials, with particular regard to TSEs, may be found in the Australian medical devices guidance document number 14, Requirements for the assessment of medical devices containing animal material, with particular regard to the minimisation of risks relating to transmitting Transmissible Spongiform Encephalopathies (TSEs) <http://www.tga.gov.au/docs/html/devguid14.htm>.