A Tale of Two Stressors in Biologic Drug Product Development: Shaking Mode and Primary Packaging

Siddhanth Hejmady; Elham Taherian; Reza Nejadnik

doi:10.1007/s11095-025-03959-4

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A Tale of Two Stressors in Biologic Drug Product Development: Shaking Mode and Primary Packaging

Journal article

Open access

Peer reviewed

A Tale of Two Stressors in Biologic Drug Product Development: Shaking Mode and Primary Packaging

Siddhanth Hejmady, Elham Taherian and Reza Nejadnik

Pharmaceutical research, Vol.43(4), pp.1305-1318

04/2026

DOI: 10.1007/s11095-025-03959-4

PMCID: PMC13179228

PMID: 41254318

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Abstract

Purpose Mechanical, interfacial, and shear stresses encountered during development, manufacturing and transportation of biologics can compromise monoclonal antibody (mAb) stability. However, most scale-down shaking models often depend solely on orbital agitation and overlook the effect of the solid-liquid interface. To study this gap, stress conditions were applied to simulate early-stage product development and real-world transportation in this work. Methodology Accordingly, the aggregation profiles of Cetuximab and Tocilizumab formulations, with and without polysorbate 80 (PS80), were systematically compared after applying horizontal and orbital shaking. Protein aggregation was assessed using orthogonal techniques such as size-exclusion chromatography, dynamic light scattering, flow imaging microscopy, ultraviolet-visible spectroscopy, and visual inspection. Results Horizontal shaking more effectively revealed Cetuximab's susceptibility to aggregation under mechanical and interfacial stress whereas orbital shaking conditions were not as discriminative. Furthermore, to explore the effect of vial surface chemistry on subsequent protein aggregation, Cetuximab was subjected to horizontal shaking stress using both untreated and silanized glass vials. Interestingly, hydrophobic silanized vials without surfactant resulted in increased Cetuximab aggregation compared to untreated vials. In contrast, Cetuximab with PS80 showed fewer aggregates in silanized vials than in glass vials. Conclusion These results underscore the value of selecting right-for-purpose agitation models and highlight the need to explore the triple interface for improving stress screening in drug product development.

Physical Sciences

Chemistry

Chemistry, Multidisciplinary

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Science & Technology

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Details

Title: Subtitle: A Tale of Two Stressors in Biologic Drug Product Development: Shaking Mode and Primary Packaging
Creators: Siddhanth Hejmady - Univ Iowa, Dept Pharmaceut Sci & Expt Therapeut, 446 Coll Pharm Bldg CPB,180 S Grand Ave, Iowa City, IA 52242 USA
Elham Taherian - Univ Iowa, Dept Pharmaceut Sci & Expt Therapeut, 446 Coll Pharm Bldg CPB,180 S Grand Ave, Iowa City, IA 52242 USA
Reza Nejadnik - University of Iowa, Pharmaceutical Sciences and Experimental Therapeutics
Resource Type: Journal article
Publication Details: Pharmaceutical research, Vol.43(4), pp.1305-1318
DOI: 10.1007/s11095-025-03959-4
PMID: 41254318
PMCID: PMC13179228
NLM abbreviation: Pharm Res
ISSN: 0724-8741
eISSN: 1573-904X
Publisher: Springer Nature
Number of pages: 14
Language: English
Electronic publication date: 11/18/2025
Date published: 04/2026
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9985091364002771

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