Scientific Reports (Jun 2022)

DoE-derived continuous and robust process for manufacturing of pharmaceutical-grade wide-range LNPs for RNA-vaccine/drug delivery

  • Kakon Nag,
  • Md. Enamul Haq Sarker,
  • Samir Kumar,
  • Habiba Khan,
  • Sourav Chakraborty,
  • Md. Jikrul Islam,
  • Juwel Chandra Baray,
  • Maksudur Rahman Khan,
  • Asif Mahmud,
  • Uttam Barman,
  • Eleus Hussain Bhuiya,
  • Mohammad Mohiuddin,
  • Naznin Sultana

DOI
https://doi.org/10.1038/s41598-022-12100-z
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 11

Abstract

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Abstract Lipid nanoparticle (LNP) technology has become extremely demanding for delivering RNA-products and other drugs. However, there is no platform to manufacture pharmaceutical-grade LNPs with desired particle size from a wide range in continuous mode. We have developed a unique platform to obtain any specific size-range of LNPs from 60 to 180 nm satisfying pharmaceutical regulatory requirements for polydispersity index, sterility, dose uniformity and bio-functionality. We applied design of experiment (DoE) methodology and identified the critical process parameters to establish the process for global application. Cross-point validation within the response map of DoE confirmed that the platform is robust to produce specific size (± 10 nm) of LNPs within the design-range. The technology is successfully transformed to production scale and validated. Products from R&D, pilot and production batches for a candidate SARS-CoV-2 mRNA-vaccine generated equivalent biological responses. The data collectively established the robustness and bio-uniformity of doses for global RNA-vaccine/drug formulation.