OLIVIER LUDEMANN-HOMBOURGER¹, PER MÖLLER², FRANCOIS KUSTER¹
1. PolyPeptide Group, Strasbourg, France
2. PolyPeptide Group, Malmö, Sweden

Abstract

This article highlights the key steps in the development and implementation of a proper purification strategy for the manufacture of peptide APIs. Our ambition is to recommend a structured methodology, including a good understanding of the separation mechanism to develop the process and to apply the latest technologies for the optimization of the purification step to reach the best performance of the manufacturing process.

INTRODUCTION

The recent publication of the 2020 FDA drug approvals shows again the growing interest of the pharmaceutical industries for oligonucleo- and pep-TIDES, representing around 10% of the new drug authorized this year (1), with two new oligonucleotides and three peptides. Over the period 2015-2019, peptides and peptides-containing molecules accounted for 7% of the total approved drugs (2).

Over 80% of the peptide currently developed are produced synthetically. 

The optimization of the synthesis process is strongly linked to the development of the right purification strategy, based on the identified critical impurities. 

As stated in a recent article (3), the development of new methodologies should minimize the number of iterations to select the optimal manufacturing strategy. The use of in-silico development tools is an emerging evolution in the practices to answer to the challenge to quickly get access to an optimized process with a Right First Time strategy.

Most of the publications related to pep ...