Critical aspects regarding the application of GPL principles to new compounds such as biotechnology products.

The safety evaluation of new products such as the biotechnology-derived pharmaceuticals (biopharmaceuticals) requires a less standardised and more flexible approach. This is basically due to the characteristics of each product, especially so as regards species specificity and immunogenicity activity. Thus, it is necessary to select the relevant animal species for toxicity testing, to evaluate the effects on the immune system, and then to develop new types of tests (e.g., in vitro tests and analytical methods). Nevertheless, also regulatory authorities (RAs) recognise that some studies/ tests may be part of the registration dossier, although good laboratory practice (GLP) compliance cannot be fully claimed. Non-compliance issues need to be clearly identified as well as their impact on the overall safety evaluation. The application of GLP principles to new tests/methods always requires their re-interpretation and adaptation and, as usual, new doubts and questions arise, e.g., the availability, need and extension of the characterisation of the reference items, including the blank matrices, as well as the feasibility, need and extension of the validation of any new test/method developed. Difficulties may well arise if the same level of application of the GLP principles to traditional analytical methods is compulsorily requested also for new test/method, especially in the case of the non-quantitative ones. Therefore, it seems necessary to evaluate the issue more in depth in order to establish a dialogue among all involved parties for a harmonised understanding and application of the GLP principles in this field.