Thermostabilize Coronavirus Vaccines: Formulation and Process Development and Rapid Scale-Up Through Modeling and QbD Experimentation

The aim is to develop vaccine lyophilization formulations and processes to thermostabilize coronavirus vaccine surrogates that pharmaceutical companies could then apply to produce vaccine stockpiles enabling a more rapid response to future outbreaks
Categories
Process control
Active Immunization Countermeasures

Industry Need

  • The COVID-19 pandemic demonstrated that the reliance on real-time manufacturing and requirements for cold chain storage for current vaccines severely limits the national response to health emergencies. 
  • Two of the current FDA-authorized COVID-19 vaccines (Pfizer & Moderna) and one vaccine in Phase III clinical trials (CureVac) are formulated as Liquid NanoParticle (LNP)-encapsulated mRNA. 
  • Lyophilization, or freeze-drying, of these vaccines would create vaccine stockpiles and reduce logistics burdens during vaccine administration. 
  • These formulations present unique challenges for freeze-drying because each formulation may require different freeze-drying conditions to ensure the vaccine's efficacy is not lost during the freeze-drying process. 


Approach

Physical Sciences Inc., NIPTE, and UMass will test LNPs and formulations to determine best practices for freeze-drying future coronavirus vaccines.   

The goals of this project are to: 

  • Identify and test candidate vaccine formulations  
  • Develop freeze-drying cycle recipes 
  • Create improvements to process development and scale-up models. 


Impacts

Develop vaccine lyophilization formulations and processes to thermostabilize coronavirus vaccine surrogates that pharmaceutical companies could leverage to produce vaccine stockpiles, enabling a more rapid response to future viral outbreaks.

Value Statement/Outcomes

This project eliminates the high-risk dependency on ultra-low temperature logistics by establishing validated lyophilization "recipes" that transform volatile liquid mRNA-Liquid NanoParticle into stable, stockpile-ready assets. Implementing these standardized freeze-drying protocols is projected to reduce global distribution and storage by 30–50% while slashing product spoilage rates by an estimated 15–20%. By shifting from reactive manufacturing to pre-validated scale-up models, the industry can compress future outbreak response timelines by 3–6 months, securing a multi-billion-dollar advantage in pandemic readiness.

Outputs/Deliverables

Defined lyoprotectant formulations that prevent significant structural changes of LNP-encapsulated mRNAs through minimizing particle size growth while maintaining encapsulation efficiency and mRNA integrity​

Demonstrated successful development of optimized lyophilization processes that reduce processing times while maintaining mRNA-LNP product quality​

Generated data sets for model inputs to be used with process development modeling software to enable process development and scale-up for both single and multi-dose product formats

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Project Lead

Physical Sciences Inc

Physical Sciences Inc

Participating Organizations

National Institute for Pharmaceutical Technology and Education, Inc (NIPTE)

National Institute for Pharmaceutical Technology and Education, Inc (NIPTE)

University of Massachusetts System

University of Massachusetts System