Due to the nature of biopharmaceuticals there needs to be a flexible, case
by case, science-based approach to preclinical safety evaluation of these products.
Generally the regulators recognise that pharmacokinetic and tissue distribution
studies in relevant species are useful for these test items but that routine
mass balance studies are not useful.
Where using radiolabelled proteins, it is important to show that the radiolabelled test product maintains activity and biological properties equivalent to that of the unlabelled material (may be an issue for radioiodinated proteins or peptides where the incorporation of the 125I may affect the tertiary structure of the product). Caution needs to be taken in interpretation of studies involving radioactive tracers incorporated into specific amino acids because of recycling of amino acids into non-drug related proteins / peptides.
Huntingdon Life Sciences have extensive experience in radioiodination of proteins and peptides for use in such studies.
As the expected consequence of metabolism of biotechnology derived pharmaceuticals
is degradation to small peptides and amino acids, metabolic pathways are generally
understood and so classical biotransformation studies are not needed.
|
