Walles, Markus (2022) A Cross Company Perspective on the Assessment of Therapeutic Protein Biotransformation. Drug metabolism and disposition, June.

Abstract

Unlike small molecules (SMs), biotransformation of therapeutic proteins (TPs), except for antibody-drug conjugates (ADCs), has not been broadly investigated and included in regulatory filings. Nevertheless, there is an expanding pool of evidence suggesting that the ever increasingly diverse modalities and complexity of the TPs than the conventional monoclonal antibodies (mAbs) can significantly benefit from the insights of biotransformation into this area of therapeutics. For instance, such biotransformation analysis of the TP affords important information on its molecular stability, which may shed light into any potential impact on binding affinity, potency, pharmacokinetics, efficacy, safety and bioanalytical strategy. This white paper is intended to summarize the current practices in studying biotransformation of TPs and related findings in the biopharmaceutical industry. A key objective is to raise the awareness of this topic which remains relatively underexplored in the development of TPs. It is hopeful that continued efforts and the cumulative data could pave the way for establishing a consensus on the biotransformation assessment of TPs in the future between the industry and regulatory authorities.

Item Type:	Article
Keywords:	biotransformation, Therapeutic proteins
Date Deposited:	05 Apr 2022 00:45
Last Modified:	05 Apr 2022 00:45
URI:	https://oak.novartis.com/id/eprint/45537