*MICHAEL THOMPSON

New Processes Mimicking the Spray drying technique for the Preparation of Thermally Stable Vaccines

Challenge: The storage and worldwide distribution of vaccines represent complex issues for pharmaceutical companies due to vaccine instability at ambient temperatures. Spray drying is an established industrial processing technology for stabilizing many products as dried powders. Although studies have shown spray drying to be promising for preparing thermally stable vaccines in order to alleviate cold chain requirements, to date, no vaccine products produced by spray drying are on the market. The main reason is that screening for the optimal spray dried formulation of vaccines is time consuming and expensive owing to the complexity of the technique.

Solution: To expedite the development of thermally stable dry powder vaccines, the research team proposed 2 screening platforms, Microplate Droplet Drying and Single Droplet Analysis, to mimic attributes of the spray drying technique, in order to minimize the costly consumption of the active biological ingredient. These platforms were evaluated for their effectiveness by testing several single and binary carbohydrate matrices for their suitability as excipients in encapsulating thermally sensitive viral-based vaccines as spray-dried powders.

Achievements/Impact: Using these two platforms, the team studied the encapsulation of three viral vectors to convert them into thermally stable powders using spray-drying techniques. A human adenoviral vector (AdHu5), and a vesicular stomatitis virus (VSV) vector were primarily used for this study, with other viral vectors tested to a smaller degree. Both viral vectors were manufactured with a green fluorescent protein (GFP) for in vitro viral activity testing. The two platforms were systematically compared with spray drying, using comparable conditions. Multiple different excipients were screened in order to encapsulate these viral vectors. The resultant data showed that neither process recapitulated the full viral activity of spray drying but both predicted excipients that were better for the thermal stability of these viral vectors. The readily implementable Single Droplet approach was recommended for future research and implementation in a company lab since the viral activities were closest to spray drying and the set up could be commercially acquired.

Overall, the Microplate Droplet Drying method is considered viable as a screening method as well. The methodologies described here represent highly promising avenues for developing thermally stable spray dried vaccines.

Principal Investigator:

Michael Thompson
McMaster University

Co-investigators

Emily Cranston
McMaster University

Zhou Xing
McMaster University

Completed Project
$300,000 / 2 years
Supported by CQDM through:
• Merck
• Pfizer
• Boehringer Ingelheim
• GSK
• Janssen
• Novartis
• Sanofi
• BL-NCE
And by co-funding partner:
• OCE