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, Md. Maksudur Rahman Khan, Asif Mahmud, Uttam Barman, Eleus Hussain Bhuiya, Muhammad M. Mohiuddin, Naznin Sultana
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.