A review in Current Opinion in Chemical Engineering in 2024 highlights how model-based approaches are critical in “accelerating vaccine manufacturing process development”, with the authors emphasising the “significance” of an integrated modelling platform for vaccine manufacturing.
“Vaccine administration is widely recognised as one of the most valuable healthcare interventions for routine immunisation and outbreaks management.”
The importance of developing “efficient and effective pharmaceutical manufacturing processes” was “underscored” by the COVID-19 pandemic as we became more acutely aware of the need for “affordable” vaccines that are available at scale and accessible in as little time as possible.
Continued challenges
The authors recognise that “remarkable advancements” in vaccine discovery science have been made but suggest that the “task of effectively scaling up laboratory-based processes for commercial manufacturing” poses a continued, significant challenge.
“The manufacturing process plays a crucial role in preserving the essential properties identified during vaccine discovery, enabling the production of substantial quantities under tightly controlled conditions for clinical trials and subsequent market supply.”
Vaccine production is “lengthy and cost costly” in nature, with process development accounting for up to 30% of the time taken for successful market introduction of a vaccine.
Innovative technology
Regulatory bodies are keen to enhance the efficiency of pharmaceutical manufacturing and have “encouraged the adoption of innovative methodologies” through Process Analytical Technology (PAT) frameworks and implementation of Quality by Design (QbD) principles. These highlight the importance of knowledge-based tools that “enable manufacturers to better understand, predict, and assure the quality of their products”.
Although model-based approaches have been “widely applied in diverse biomanufacturing domains” for enhanced production efficiency, vaccine biomanufacturing has “not kept pace”. The paper suggests that this is partly attributable to the “ever-evolving landscape” of vaccine types. Furthermore, regulatory concerns “contribute to this constraint”.
Therefore, the authors present an “overview of recent advances in model-based approaches for the purpose of improving process development”, giving an “outlook” on how an integrated model-based approach could influence vaccine manufacturing in the future.
Why incorporate modelling?
The paper identifies “several distinct advantages” to modelling in the context of process development. For example, it offers a “robust framework for understanding the underlying mechanisms of the process”. It can also be a “valuable aid” in the planning and designing of experimental setups and in the evaluation of value propositions and associated risks of new products and processes. Validated models can be applied to the development of advanced control strategies in later stages, and models have recently become popular for the prediction of environmental impacts of processes.
“Models have far-reaching implications beyond process development, particularly in the manufacturing stage. They are the key elements of digital twin and real-time model-based control strategies and can significantly improve the efficiency of manufacturing processes when integrated with real-time data.”
Modelling approaches range from the mechanistic to the empirical, data-driven to hybrid. The latter has emerged as an “effective approach” that combines the “predictive capabilities of mechanistic models” with the “efficiency of data-driven models”.
“This integration allows for minimising the amount of data needed for model development while ensuring the inclusion of physical relevance to key processes.”
A case study in integration
“To achieve an integrated model, a systematic and holistic approach is necessary for harmonisation of the unit operations. This includes interface compatibility, availability and robustness of parameter outputs and inputs, production scales, as well as modes of operations.”
Indeed, the authors state that “failure to couple the unit operations together in a simulation model” is a significant risk in bioprocess modelling. Therefore, it is “essential to comprehensively assess the issues related to heterogeneity, inconsistency, and varying model accuracy across unit processes.” A presented case study is the Inno4Vac project (Innovations to accelerate vaccine development and manufacture).
A key focus of the project is subtopic 4 (ST4), which considers the establishment of a modular open-source computational platform for in silico modelling of protein subunit vaccine biomanufacturing and stability testing. ST4 comprises 5 work packages (WPs) in pursuit of the following objectives:
- WP16: develop stability prediction models for vaccine manufacturing using linear and nonlinear equations and integrate them into a global biomanufacturing platform.
- WP17: establish a cloud-based platform to assess the performance and robustness of biomanufacturing processes, with a specific emphasis on scaling up and down in the production of vaccines using E.coli.
- WP18: create digital twins for key purification units, apply advanced in silico analysis and design tools, and enable real-time control to optimise downstream processing, especially for scale changes.
- WP19: validate the predictive capabilities of in silico models for vaccine stability, unit operations in protein subunit vaccine manufacturing, and control modules developed in WP18.
- WP20: initiate a regulatory dialogue to engage with authorities, paving the way for the future inclusion of predictive modelling in chemistry, manufacturing, and control (CMC) dossiers for vaccines.
The authors conclude that model-based approaches offer “significant opportunities for enhancing vaccine production” but highlight the value of developing an integrated modelling platform for biopharmaceutical manufacturing as exemplified by Inno4Vac.
Do you use modelling in your work, or did you find the publication a helpful insight into how model-based approaches could be implemented in vaccine development? For more on improving and invigorating vaccine manufacturing processes, do join us at the Congress in Washington this April or subscribe to our newsletters here.
