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

被引：2

作者：

Morar-Mitrica, Sorina ^{[1
]}

Pohl, Thomas ^{[2
]}

Theisen, Dietmar ^{[3
,12
]}

Boll, Bjorn ^{[2
,4
]}

Bechtold-Peters, Karoline ^{[1
]}

Schipflinger, Reinhard ^{[5
]}

Beyer, Beate ^{[6
]}

Zierow, Swen ^{[6
]}

Kammuller, Michael ^{[7
]}

Pribil, Andreas ^{[8
]}

Schmelzer, Bernhard ^{[9
]}

Boehm, Stephan ^{[10
]}

Goetti, Micheline ^{[11
,13
]}

Serno, Tim ^{[1
]}

机构：

[1] Novartis Pharmaceut, Biol Drug Prod Dev, Basel, Switzerland

[2] Novartis Pharmaceut, Biol Analyt Dev, Basel, Switzerland

[3] BioNTech SE, Global Regulatory Affairs, Mainz, Germany

[4] Ten23 Hlth, Basel, Switzerland

[5] Sandoz, Global Project Management Off, Schaftenau, Austria

[6] Sandoz, Biol Drug Subst Dev, Schaftenau, Austria

[7] Novartis Inst Biomed Res, Translat Med Preclin Safety, Basel, Switzerland

[8] Novartis, Global PAT & Stat MS&T, Schaftenau, Austria

[9] Sandoz, Biol Analyt Dev Stat & Modeling, Schaftenau, Austria

[10] Sandoz, Biol Drug Prod Dev, Schaftenau, Austria

[11] Adv Accelerator Applicator, Geneva, Switzerland

[12] Novartis Pharmaceut, Regulatory CMC Biol, Basel, Switzerland

[13] Sandoz, Novartis Pharma, NTO Qual, Basel, Switzerland

来源：

JOURNAL OF PHARMACEUTICAL SCIENCES | 2023年 / 112卷 / 05期

关键词：

Protein aggregation; Stability; Particle size; Analysis; Database; MONOCLONAL-ANTIBODY; AGGREGATION; PERSPECTIVE; ADSORPTION; SHEAR;

D O I：

10.1016/j.xphs.2023.01.023

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. & COPY; 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

引用

页码：1476 / 1484

页数：9