Squalene Emulsion Manufacturing Process Scale-Up for Enhanced Global Pandemic Response

Abstract

Squalene emulsions are among the most widely employed vaccine adjuvant formulations. Among the demonstrated benefits of squalene emulsions is the ability to enable vaccine antigen dose sparing, an important consideration for pandemic response. In order to increase pandemic response capabilities, it is desirable to scale up adjuvant manufacturing processes. We describe innovative process enhancements that enabled the scale-up of bulk stable squalene emulsion (SE) manufacturing capacity from a 3000- to 5,000,000-dose batch size. Manufacture of concentrated bulk along with the accompanying viscosity change in the continuous phase resulted in a ≥25-fold process efficiency enhancement. Process streamlining and implementation of single-use biocontainers resulted in reduced space requirements, fewer unit operations, and minimization of cleaning requirements. Emulsion physicochemical characteristics were measured by dynamic light scattering, laser diffraction, and HPLC with charged aerosol detection. The newly developed full-scale process was demonstrated by producing two 5,000,000-dose batches of bulk concentrated SE. A scale-up of adjuvant manufacturing capacity through process innovation enables more efficient production capabilities for pandemic response.

“World in motion” – emulsion adjuvants rising to meet the pandemic challenges

“…SE was evaluated in clinical studies of pandemic H1N1 influenza but was never licensed. However, the manufacturing process for SE was successfully transferred to alternative sites to promote local vaccine production 85 , and innovations in its manufacturing have continued, with a view to the eventual global production of pandemic influenza vaccines 7 , 86 .…”

Using Dual Toll-like Receptor Agonism to Drive Th1-Biased Response in a Squalene- and α-Tocopherol-Containing Emulsion for a More Effective SARS-CoV-2 Vaccine

“…The large variation in INI-2002 recovery was likely due to a combination of a low absorbance of the molecule at the detection wavelength and the low target amount of INI-2002, which tested the lower limits of detectability using our given protocol and detector. Additionally, clinical-grade emulsions are often made at a higher concentration and diluted down as part of the manufacturing [ 64 ] or administration, so it may be possible to improve the detection of INI-2002 by increasing the amount of all compounds used.…”