Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Replacement, Reduction, Refinement of Animal Testing in Quality Control of Medicinal Products in the EU ***

Dr. Ulrich Feil (Abschlußjahr: 2009)

Summary
Language: English
There is an ethical dilemma concerning medicinal products and laboratory animals. In one hand we have the moral obligation to produce medicinal products and to guarantee safety and efficacy for the welfare of humans and also animals. On the other hand, we use large numbers of laboratory animals. Although society as such accepts the use of animals for these purposes, there is a strong public incentive that this situation is only acceptable in case no alternatives are available. Therefore, there is a strong pressure to combining product safety and efficacy and animal welfare.
In the field of biological medicine, a large number of tests, mainly those for safety, and also those for assays, relay on results based on animal testing. A significant number of animals are required for quality control and safety testing. The requirements for these testing are laid down in the European Pharmacopoeia and in relevant guidelines. The majority of these animal tests are described in various product-specific or general monographs. In the Pharmacopoeia the possibility of replacing, refining or reducing animal tests is mentioned in a number of general or specific monographs. In the recent years measures ware taken to implement new specifications, methods, and concepts such as in process controls, suitability tests, quality assurance, performance testing. A considerable number of achievements have been made in the last few decades and studies are ongoing.
Important efforts were made in both areas: the development of new manufacturing tools, including rules of Good Manufacturing Practice (GMP) and quality assurance combined with another important development, namely the advances in the field of analysis of biological products.
The implementation of the alternatives concerning the safety and potency testing is now in place for several years and did not jeopardize the safety of the medicinal products placed on the market. This is the consequence of the application of alternative test methods only when the manufacturing consistency has been established and/or a suitable validation has been carried out. In some cases the in vivo test remains the reference test or the gold standard to support main manufacturing changes. These alternatives are more specific, targeting the specific toxic component and are also much more sensitive. The implementation phase is very long and for implementation a regulatory variation is mandatory even if the alternative is included in the regulations.
In the EU a significant reduction of the animal tests in the recent years has been observed. The implementation delay of some alternative tests or the slow progress in recognizing new alternatives represents difficulties considering the possible application of these alternatives in countries outside EU. To overcome these issues, the proposals could be the enhancement of the initiatives for a global harmonization endorsed by international organisations.
Pages: 66