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Forced degradation, also known as stress testing, is used throughout pharmaceutical development for many purposes including assessing the comparability of biopharmaceutical products according to ICH Guideline Q5E. These formal comparability studies, the results of which are submitted to health authorities, investigate potential impacts of manufacturing process changes on the quality, safety, and efficacy of the drug. Despite the wide use of forced degradation in comparability assessments, detailed guidance on the design and interpretation of such studies is scarce. The BioPhorum Development Group is an industry-wide consortium enabling networking and sharing of common practices for the development of biopharmaceuticals. The BioPhorum Development Group Forced Degradation Workstream recently conducted several group discussions and a benchmarking survey to understand current industry approaches for the use of forced degradation studies to assess comparability of protein-based biopharmaceuticals. The results provide insight into the design of forced degradation studies, analytical characterization and testing strategies, data evaluation criteria, as well as some considerations and differences for non-platform modalities (e.g., non-traditional mAbs). This article presents survey responses from several global companies of various sizes and provides an industry perspective and experience regarding the practicalities of using forced degradation to assess comparability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Unlabelled: The aim of this work is to understand and achieve low fouling surfaces by mixing two oppositely charged polysaccharides through layer-by-layer (LBL) assembly. Diethylaminoethyl-dextran hydrochloride and alginate were employed as a model system to build LBL films. A surface plasmon resonance (SPR) biosensor was used to measure quantitatively the adsorption behavior of charged macromolecules during LBL buildup and the protein adsorption behavior of each deposited bilayer in situ in real time accordingly. Results show that LBL films have lower protein adsorption as the films are constructed above the substrate surface. These LBL films eventually reach very low fouling when they are sufficiently far from the substrate surface, where the substrate surface effect is minimized and bilayers consisting of positively and negatively charged marcromolecules are uniformly mixed. Single proteins, undiluted human blood serum and plasma and cells were tested for adsorption to LBL films with similar trends. To verify the generality of these findings, alginates of low and high molecular weights and carboxymethylcellulose as a substitute to alginate were studied with similar trends observed. These results demonstrate that oppositely charged polymers, when uniformly mixed, are able to achieve low fouling properties. Findings from this work will provide a fundamental understanding of and design principles on how to build nonfouling LBL films., Statement of Significance: We demonstrate that protein adsorption decreases with the increase of bilayer numbers. Results indicate that oppositely charged components tend to be uniformly mixed and distinct change layers in classical layer-by-layer (LBL) theories no longer exist as LBL films are sufficiently far from the substrate surface. Findings from this work provide a fundamental understanding of and design principles on how to build nonfouling LBL films., (Published by Elsevier Ltd.)