A new scaleable freeze-thaw technology for bulk protein solutions

Area of Science:

• Biopharmaceutical processing
• Protein formulation
• Cryobiology

Background:

• Freeze-thaw processes are critical for biopharmaceutical development but scaling them presents challenges.
• Current methods often lack predictable scalability, impacting process efficiency and product quality.
• Recombinant human growth hormone (rhGH) is a sensitive biologic requiring careful handling during storage and processing.

Purpose of the Study:

• To introduce and validate a new freeze-thaw method using rectangular containers for improved scalability.
• To assess the impact of this method on the quality and stability of recombinant human growth hormone (rhGH) solutions.
• To evaluate the potential for transferring this freeze-thaw technology to manufacturing.

Main Methods:

• Experimental freeze-thaw of purified rhGH solutions in miniature and pilot-scale rectangular containers.
• Computational fluid dynamics (CFD) simulations to model and compare freeze processes.
• Protein quality assessment using dynamic light scattering, circular dichroism, size-exclusion, and reverse-phase HPLC.

Main Results:

• The rectangular container geometry facilitates linear scale-up based on equivalent temperature-time profiles.
• rhGH solutions (approx. 30 mg/ml) remained undamaged after up to five freeze-thaw cycles.
• CFD simulations correlated well with experimental freeze-thaw data.
• A nitrogen blast chest-freezer was designed and evaluated as part of the process.

Conclusions:

• The novel rectangular container freeze-thaw method is applicable and scalable for biopharmaceutical processing.
• This approach effectively preserves the quality of rhGH solutions, demonstrating its suitability for bulk processing.
• The method shows promise for seamless transfer from development to manufacturing scales.