Influence of Production Process and Scale on Quality of Polypeptide Drugs: a Case Study on GLP-1 Analogs

Pharmaceutical Research
Arne StabyDésirée J Asgreen

Abstract

Manufacturing processes for polypeptide/protein drugs are designed to ensure robust quality, efficacy and safety. Process differences introduced by follow-on manufacturers may result in changes in quality and clinical outcomes. This study investigated the impact of production methods on the stability and impurities of liraglutide and semaglutide drug substances/products, and the potential impact on drug quality, efficacy and safety. State-of-the-art analytical methods were used to compare physical and chemical stability, and impurity profiles of drug substances/products from different suppliers. Identified polypeptide-related impurities were evaluated for immunogenicity potential by in silico T cell epitope prediction. Semaglutide immunogenicity in clinical trials (SUSTAIN) was evaluated using a tiered antibody analysis. Manufacturing scale and process strongly impacted the physical stability of the products. Trace metals increased high-molecular-weight protein formation for liraglutide and semaglutide. Synthetic and recombinant liraglutide produced by five suppliers had distinct impurity profiles compared with the originator. In silico evaluation suggested that new impurities could be immunogenic. Immunogenicity of semaglutide...Continue Reading

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Citations

Oct 22, 2020·Journal of the American Society for Mass Spectrometry·Simon K GammelgaardPeter Kresten Nielsen

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Methods Mentioned

BETA
glycosylation
acylation
electron microscopy
Size Exclusion Chromatography
fluorescence assay
deamidation

Clinical Trials Mentioned

NCT02054897
NCT01885208
NCT02128932
NCT01930188
NCT02305381
NCT02207374
NCT02254291
NCT01720446

Software Mentioned

NetMHCIIpan
ImageJ
SUSTAIN
Originator

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