An Intra-Company Analysis of Inherent Particles in Biologicals Shapes the Protein Particle Mitigation Strategy Across Development Stages

To better understand protein aggregation and inherent particle formation in the biologics pipeline at Novartis, a cross-functional team collected and analyzed historical protein particle issues. Inherent particle occurrences from the past 10 years were systematically captured in a protein particle d...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of pharmaceutical sciences Vol. 112; no. 5; p. 1476
Main Authors:	Morar-Mitrica, Sorina, Pohl, Thomas, Theisen, Dietmar, Boll, Björn, Bechtold-Peters, Karoline, Schipflinger, Reinhard, Beyer, Beate, Zierow, Swen, Kammüller, Michael, Pribil, Andreas, Schmelzer, Bernhard, Boehm, Stephan, Goetti, Micheline, Serno, Tim
Format:	Journal Article
Language:	English
Published:	United States 01-05-2023
Subjects:	Antibodies, Monoclonal Biological Products Particle Size Protein Aggregates Database Particle size Protein aggregation Stability Analysis
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	To better understand protein aggregation and inherent particle formation in the biologics pipeline at Novartis, a cross-functional team collected and analyzed historical protein particle issues. Inherent particle occurrences from the past 10 years were systematically captured in a protein particle database. Where the root cause was identified, a number of product attributes (such as development stage, process step, or protein format) were trended. Several key themes were revealed: 1) there was a higher propensity for inherent particle formation with non-mAbs than with mAbs; 2) the majority of particles were detected following manufacturing at scale, and were not predicted by the small-scale studies; 3) most issues were related to visible particles, followed by subvisible particles; 4) 50% of the issues were manufacturing related. These learnings became the foundation of a particle mitigation strategy across development and technical transfer, and resulted in a set of preventive actions. Overall, this study provides further insight into a recognized industry challenge and hopes to inspire the biopharmaceutical industry to transparently share their experiences with inherent particles formation.
ISSN:	1520-6017
DOI:	10.1016/j.xphs.2023.01.023