The choice of mixing technology can have a significant impact on both process performance and product quality when manufacturing biologic drug products. A recent study compared three single-use mixing approaches to determine how effectively they mix formulations and how much mechanical stress they impose on proteins.
The researchers compared top-mounted impeller (TMM), bottom-mounted impeller (BMM) and conventional magnetic stirring (MS) in drug-substance bottles. Mixing efficiency was assessed by measuring dissolution time under different conditions, including container size, fill volume and impeller tip speed. Mechanical stress was evaluated using a model protein and supported by computational fluid dynamics simulations.
The results showed that dissolution time decreased with increasing tip speed and impeller-to-bottle diameter ratio. Both impeller-based systems consistently provided better mixing performance than magnetic stirring. The magnetic stirrer, in particular, delivered insufficient mixing in some configurations.
The study also demonstrated that mixing can affect protein quality through mechanical stress. The impact depended on the mixer type and fill volume. Higher fill volumes reduced the adverse effects on the model protein. Overall, the magnetic stirrer produced greater and more variable effects on protein quality than the bottom-mounted impeller.
Conclusion
Overall, the choice of single-use mixing technology matters both for achieving efficient mixing and for protecting the quality of biologic drugs. The newer bottom-mounted impeller performed particularly well, combining efficient mixing with less adverse impact on the model protein than the magnetic stirrer.
The researchers therefore conclude that their data can help formulation and process-development scientists select and scale up mixing systems based on measurable performance rather than simply choosing a conventional technology.