From R&D to production: Scale-out of continuous spin-freeze-drying for a PEGylated peptide formulation

Scale-out is critical for translating continuous spin-freeze-drying from development to GMP-relevant manufacturing. In this study, a continuous spin-freeze-drying process for a model PEGylated peptide formulation was transferred from a single-vial-lab-scale R&D unit (RheaLyo™ Mono) to a GMP-compatible prototype line (GMP-Flex™). Identical spin-freezing and drying settings were applied on both platforms to directly assess the reproducibility of process performance during scale-out. Product temperature profiles during freezing and drying aligned closely between RheaLyo™ Mono and GMP-Flex™, indicating comparable thermal histories across scales. Product quality was assessed by cake appearance, residual moisture content, peptide concentration by RP-HPLC and monomer levels by SEC. All samples formed intact cakes without signs of collapse and maintained monomer levels close to 100 percent, indicating no detectable aggregation upon transfer. Residual moisture contents for both platforms were within the same overall range and met the predefined target of 0.3-0.6%. Residual moisture levels on the GMP-Flex™ prototype showed no timing-dependent trend over the production run, confirming stable, steady-state drying performance throughout continuous production. Overall, these results demonstrate for the first time the successful scale-out of continuous spin-freeze-drying under the matched process conditions while maintaining consistent product quality.