The quest for down scale representativeness: how to exploit CFD to design a shear study for vaccines

Area of Science:

• Biopharmaceutical Manufacturing
• Chemical Engineering
• Vaccine Development

Background:

• Designing representative scale-down systems (SDS) is critical for vaccine drug product (DP) process characterization.
• Stirred tank reactors (STRs) are commonly used in DP formulation, requiring careful scale-down to mimic manufacturing conditions.
• Understanding shear history within SDS is essential for maintaining DP quality attributes.

Purpose of the Study:

• To evaluate computational fluid dynamics (CFD) for designing a representative SDS for an aluminum-adjuvanted vaccine DP.
• To compare two stirring speed down-scale strategies: tip speed equivalence and rotating shear.
• To determine the optimal scaling approach for accurately reflecting manufacturing scale shear conditions.

Main Methods:

• Utilized CFD simulations to analyze process engineer parameters (PEP) in STRs.
• Employed the 'number of passages' concept to study shear history in the SDS.
• Investigated tip speed equivalence and rotating shear as scaling criteria for SDS design.

Main Results:

• CFD simulations indicated that tip speed equivalence creates a worst-case SDS regarding shear.
• The rotating shear scaling approach demonstrated potential for designing a more representative SDS.
• Monitoring 'In Vitro Relative Potency' highlighted the impact of scaling strategy on DP Critical Quality Attributes.

Conclusions:

• The choice of scaling-down approach significantly impacts the representativeness of the SDS for process characterization.
• Rotating shear offers a promising alternative to traditional tip speed equivalence for SDS design in vaccine manufacturing.
• Accurate SDS design using appropriate scaling criteria is crucial for reliable process development and validation.