Secrets of Batch Process Scale-Up

Ensuring Effective Translation of Laboratory Processes to Pilot Plant Scale.

About this course

Operating a commercially viable chemical process requires a good chemical synthesis to start with, but is also subject to the interplay of a myriad of important physical phenomena - heat transfer, mass transfer, fluid flow, etc. which are traditionally the realm of the chemical engineer. An understanding of these scale-up phenomena is crucial for the laboratory development of processes that will scale successfully.

This course presents an overview of these issues and examines their impact on process operation in the pilot plant and beyond, including scale-up considerations for route selection, raw material charging, reaction steps, workup, crystallization, product isolation, drying, etc. Common bench techniques for each of these steps are contrasted to the safety and operability criteria for successful pilot plant operation. Numerous examples and case histories are presented, along with tips and techniques for operators and experimenters. Heavy emphasis is placed on process safety.

An underlying goal of the course is improving communication and mutual understanding between development team members of different backgrounds; thus, the course is appropriate for synthetic chemists, process development chemists and process engineers with limited pilot plant experience who wish to learn more about the potential pitfalls of scale-up in process development. The course complements the more chemistry-focused Scientific Update course "Chemical Development and Scale-Up in the Fine Chemical and Pharmaceutical Industries".

Upon completion of the course, participants will be better equipped to:

* Assess process safety and scaleability
* Identify process operations that may be problematic on scale-up
* Design processes that will minimize or avoid scale-up issues
* Select operating methods and equipment for effective scale-up
* Calculate heat removal rates and safe rates of addition of reagents
* Determine mixing requirements for scale-up
* Design crystallizations which can be successfully operated at scale.
* Predict the filterability of solid products upon scale-up.
* Minimize the effects of scale-up on yield, selectivity and product purity.

Course Outline

Process Design for Scale-Up: Process development strategies, Importance of engineering in PDs.

Scale-Up - An Overview: Role of the Pilot Plant, Overview of scale-up issues, Technology transfer issues.

Batch Reactors: Typical plant operations and equipment, Characteristics of batch operations.

Raw Materials: Raw material and route selection, Large-scale charging methods and issues

Temperature Control: Large scale temperature control, Heat transfer in batch reactors, Controlling exothermic reactions.

Following Reaction Progress: Reaction endpoint, determination, Sampling methods / issues, On-line analytical techniques.

Agitation and Mixing: Large scale mixing equipment, Mixing limited reaction, Mixing scale-up / scale-down

Quench & Work-Up: Liquid-liquid extractions, Phase continuity issues and emulsions

Distillation & Stripping: Differential distillation, Azeotropes and solvent exchange

Crystallization and Precipitation: Basic principles / yield estimation, Controlling supersaturation, Scale-up issues

Product Isolation and Drying: Large-scale solid-liquid separations, Filtration and drying equipment, Filtration and drying modeling

Process Hazards and Safety Assessment: Common hazards in large-scale processing, Process hazard assessments and evaluations