Testing new pharmaceuticals after the 2006 UK drug trail tragedy.
European Journal of Hospital Pharmacy Practice, 13, 22-24 (2007)
With developments in recombinant DNA technology and supportive platforms, pharmaceutical companies are increasingly investing in the development of biotechnology-based products for clinical use . There are, however, ways in which preclinical evaluation of these products differs from that of traditional small chemical drugs. In particular, while lack of target protein sequences conservation and functional homology between the human and animal proteins and immunogenicity can restrict the choice of test species, the absorption, distribution, metabolism and excretion (ADME) profile of proteinaceous therapeutics is easier to predict than that of chemical compounds and is less likely to be subject to species variation. Nevertheless, despite good specificity for the desired target, protein therapeutics can potentially make numerous, poorly understood and undesirable off-target interactions with many of these relying on the nature of post-translational modification. The situation is further exacerbated by the fact that whether the primary mechanism of action is stimulatory or not, there may be any number of distinct non-specific effects. These characteristics are particularly problematic for monoclonal antibodies.