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Protein Interfacial Instability of Mixing and Lyophilization During Drug Product Manufacturing Process Scale-Up and Tech Transfer

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Protein Instability at Interfaces During Drug Product Development

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 43))

Abstract

Biotherapeutic product manufacturing is a complicated process that includes various unit operations, such as freeze and thaw, compounding, filtration, filling, lyophilization, inspection, packaging, storage, and transportation. During process steps in those unit operations, protein molecules may encounter stresses like shear stress and interfacial stress. These stresses could potentially negatively impact the drug product quality attributes, including formation of protein aggregates, formation of particles, or loss of protein due to adsorptions at the interface. Therefore, it is important to have a clear understanding of protein interfacial instability during drug product manufacturing. In this chapter, we will discuss in more details about various stresses that proteins encountered in the mixing and lyophilization unit operations, the relationship between the interfacial stress and protein stability, and explore strategies and best practices in order to evaluate and minimize the interfacial stress.

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Abbreviations

ADC:

Antibody-drug conjugate

BSA:

Bovine serum albumin

CFD:

Computation fluid dynamic

CMC:

Critical micelle concentration

CMO:

Contract Manufacturing Organization

DSC:

Differential scanning calorimetry

ESCA:

Electron spectroscopy for chemical analysis

GMP:

Good manufacturing practice

HCl:

Hydrochloric acid

hGH:

Human growth hormone

IgG:

Immunoglobulin

KGF:

Keratinocyte growth factor

LDH:

Lactate dehydrogenase

PAR:

Proven acceptable range

PGK:

Phosphoglycerate kinase

rhGH:

Recombinant human growth hormone

SSA:

Specific surface area

SUT:

Single-use technology

w/v:

Weight/volume

XPS:

X-ray photoelectron spectroscopy

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Author information

Authors and Affiliations

  1. CMC Development and Manufacturing, WuXi Biologics, Boston, MA, USA

    Stuart Wang

  2. Drug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USA

    Weixian Shi & Xiaodong Chen

Authors
  1. Stuart Wang
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  2. Weixian Shi
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  3. Xiaodong Chen
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Corresponding author

Correspondence to Xiaodong Chen .

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Editors and Affiliations

  1. Department of Formulation Development Nevakar Inc., Bridgewater, NJ, USA

    Jinjiang Li

  2. Drug Product Development, Bristol Myers Squibb, New Brunswick, NJ, USA

    Mary E. Krause

  3. Chemical Engineering, The City College of New York - CUNY, New York, NY, USA

    Raymond Tu

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Wang, S., Shi, W., Chen, X. (2021). Protein Interfacial Instability of Mixing and Lyophilization During Drug Product Manufacturing Process Scale-Up and Tech Transfer. In: Li, J., Krause, M.E., Tu, R. (eds) Protein Instability at Interfaces During Drug Product Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 43. Springer, Cham. https://doi.org/10.1007/978-3-030-57177-1_9

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