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Large-scale crystallization as an intermediate processing step in insulin downstream process: explored advantages and identified tool for process intensification

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Abstract

The rising global prevalence of diabetes and increasing demand for insulin, calls for an increase in accessibility and affordability of insulin drugs through efficient and cost-effective manufacturing processes. Often downstream operations become manufacturing bottlenecks while processing a high volume of product. Thus, process integration and intensification play an important role in reducing process steps and time, volume reduction, and lower equipment footprints, which brings additional process efficiencies and lowers the production cost. Manufacturers thrive to optimize existing unit operation to maximize its benefit replacing with simple but different efficient technologies. In this manuscript, the typical property of insulin in forming the pH-dependent zinc-insulin complex is explored. The benefit of zinc chloride precipitation/crystallization has been shown to increase the in-process product purity by reducing the product and process-related impurities. Incorporation of such unit operation in the insulin process has also a clear potential for replacing the high cost involved capture chromatography step. Same time, the reduction in volume of operation, buffer consumption, equipment footprint, and capabilities of product long time storage brings manufacturing flexibility and efficiencies. The data and capabilities of simple operation captured here would be significantly helpful for insulins and other biosimilar manufacturer to make progresses on cost-effective productions.

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Abbreviations

IP :

Insulin precursor

IME :

Insulin methyl ester

HCP :

Host cells proteins

HC-DNA :

Host cell DNA

RT :

Retention time

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Acknowledgements

We thank the process and characterization groups of Research and Development (RND) of Biocon Biologics for their technical support and suggestions.

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  1. Biocon Biologics Limited (BBL), Biocon Research Center (BRC), Biocon Park, Plot No. 2 & 3, Bommasandra Industrial Estate, IV Phase, Bommasandra Jigani Link Road, Bangalore, 560 099, India

    Partha Hazra, Madhavan Buddha, Chinnappa Reddy & Indranil Gupta

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Hazra, P., Buddha, M., Reddy, C. et al. Large-scale crystallization as an intermediate processing step in insulin downstream process: explored advantages and identified tool for process intensification. Bioprocess Biosyst Eng 46, 1765–1776 (2023). https://doi.org/10.1007/s00449-023-02931-z

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