mAb Process Scale-Up

Scaling introduces higher buffer and media demands, increased storage needs, and expectations for consistency across batches. Teams must adapt early-stage productivity to larger volumes while maintaining cGMP requirements. Managing space, coordinating supply, and controlling process variability become increasingly important as production progresses

Upstream scale-up while maintaining productivity and consistent batch performance involves using scalable bioreactor platforms and automation, along with optimized media and feeds as volumes increase. Ease of transfer across vessel sizes from bench to production supports reproducible scale-up and helps teams meet milestones.

Clarification systems that manage larger volumes, followed by ProA capture and polishing with AEX, CEX, and HIC resins, support early impurity reduction. As volumes rise, buffer use and facility constraints can become limiting; chromatography platforms designed for higher throughput help maintain consistent purification outcomes.

Larger-scale operations require addressing storage, labor, and scheduling pressures. Ready-to-use or made-to-order (MTO) liquids help reduce footprint and preparation steps while supporting predictable supply planning. This approach can minimize operational burden and help avoid delays when buffer preparation becomes a bottleneck in large-scale operations.

Detecting low-level impurities is important during scale-up. Upstream tools help identify mycoplasma, while downstream workflows focus on residual DNA, proteins, and viral contaminants. Using PCR and dPCR methods helps achieve low limits of quantification (LOQ) and effectively meet compliance requirements.

Viral inactivation is positioned between capture and polishing. It typically involves holding the mAb drug substance at low pH for 30–60 minutes, then neutralizing with a base. Because low pH can induce aggregation, gentle mixing and defined buffers help maintain product integrity at scale.

Single-use technologies help reduce space, cleaning, and buffer preparation demands. The DynaDrive System supports higher volumes in a smaller footprint. The DynaSpin Centrifuge can lessen process liquid and filter use. The DynaChrom System enables in-line dilution and concentrate usage to reduce buffer preparation and storage needs during commercial production.

When handling the final stages of mAb drug substance and product, container durability and compatibility with sterilized operations help maintain product safety. Single-use BPCs, engineered fill-finish formats, and low-particulate bottles support consistency and reduce handling risk as drug substance moves through processing and distribution steps.