Developing a Batch Isolation Procedure and Running It in an Automated Semicontinuous Unit: AWL CFD25 Case Study.

Area of Science:

• Chemical Engineering
• Pharmaceutical Manufacturing
• Process Development

Background:

• Transitioning from laboratory to continuous manufacturing presents challenges in developing adaptable process strategies.
• Current industrial practice involves batch optimization followed by parameter transfer, often requiring extensive re-evaluation for different equipment or mechanisms, increasing costs and time.
• The need for a unified approach to optimize isolation in batch and scale to continuous or semicontinuous processes is critical.

Purpose of the Study:

• To evaluate the CFD25 device as a tool for developing and transferring isolation strategies from batch to semicontinuous pharmaceutical manufacturing.
• To investigate the impact of input slurry properties (solid loading, particle size, solvent) on filtration and product characteristics.
• To assess the consistency and comparability of isolated product properties between batch development and semicontinuous production.

Main Methods:

• Utilized a d-optimal screening design of experiments (DoE) to optimize batch isolation conditions using the CFD25 device.
• Investigated various crystallization and wash solvents, including impurities, to mimic real-world isolation scenarios.
• Transferred the optimized batch strategy to a semicontinuous run on the same CFD25 equipment, measuring key performance indicators like throughput, cake resistance, purity, and residual solvent content.

Main Results:

• The CFD25 successfully enabled both batch optimization and semicontinuous production using identical process parameters without equipment modification.
• Isolated product properties from the semicontinuous run were generally comparable to those developed in batch, validating the transferability of the DoE-derived strategy.
• Minor variations in residual solvent content were observed in semicontinuous runs, attributed to filter plate blockage, but overall mean properties remained consistent.

Conclusions:

• The CFD25 is a versatile tool for developing new chemical entity isolation strategies in batch and scaling directly to semicontinuous active pharmaceutical ingredient production.
• The DoE approach effectively predicted and guided the isolation strategy, demonstrating successful transferability to a semicontinuous process.
• This integrated approach significantly reduces R&D costs, time, and material consumption associated with process scale-up.