Critical aspects in implementing the OECD monograph No. 14 "the application of the principles of GLP to in vitro studies".

The Organisation for Economic Cooperation and Development (OEC D) principles of good laboratory practice (GLP) were originally developed for application to animal-based toxicology studies. On the other hand, more and more studies involving in vitro test systems are performed to produce data on the safety of chemicals with respect to human health and the environment. Therefore, national legislation usually requires that the in vitro studies are conducted in compliance with the GLP principles. Furthermore, developments in the area of toxicogenomics, toxicoproteomics, toxicometabonomics and various high throughput screening techniques will also enhance the importance of in vitro methodologies for safety testing. The OEC D principles of GLP require that safety studies, independent of their type, are planned, conducted, recorded, reported, and archived in a way that they can be inspected by the GLP monitoring authorities and scientifically evaluated by the receiving authorities. Some critical aspects and pitfalls are discussed as regards the proper application and interpretation of the GLP principles for the organisation and management of in vitro studies. Organisational charts and responsibilities of test facilities (TFs) involved in single or multisite studies are sometimes dysfunctioning because there is a lack of traceability in reporting and communication lines. Manipulation of cell and tissue cultures of different test systems should be separated and performed under aseptic conditions to prevent cross-contamination. Characterization and environmental conditions under which the test systems are manipulated and stored are critical in in vitro studies. Another important pitfall is the lack of description in the experimental design concerning the use of any internal control items to control bias and to evaluate the performance of the test system. Finally, it is observed that samples of long-term preservable test systems are not always retained or only for a short time which can lead to a lack of confirmation of test system identity and/or reconstructability of the study.