Received for publication August 9, 2006.
Revised September 29, 2006.
Accepted for publication September 29, 2006.

PEGylated proteins: evaluation of their safety in the absence of definitive metabolism studies

Abstract

During the development of any PEGylated protein or peptide toxicology in relevant species will be conducted prior to human exposure. Normally comprehensive metabolism data accompany the toxicity studies for a small molecule. We have examined if such studies would be relevant in the safety assessment of PEGylated material. Literature data indicate that the PEG associated with a biological molecule should provide no extra concern as the exposure : toxicity relationship of PEG in animals and human has been thoroughly investigated and metabolism / excretion of PEG is well understood. Based on the comparisons of PEG exposure from PEGylated biological products and the exposures of PEG associated with toxicity in human the therapeutic index is large (approximately 600 fold or greater). Therefore, assuming toxicological evaluation of a biological molecule of interest is complete and satisfactory therapeutic windows are achieved the data contained in this review indicate that the PEG associated with a protein or other biological molecule does not represent an additional un-quantified risk to humans.

Key words: chemical toxicology, chronic toxicity, drug disposition, drug toxicity, toxicity, toxicity testing, toxicology