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In-House Training

Secrets of Batch Process Scale-Up

Tutors: Francis X. McConville

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”.

Course outline

Process Design for Scale-Up
Process development strategies
Importance of engineering in PDsScale-Up – An Overview
Role of the Pilot Plant
Overview of scale-up issues
Technology transfer issuesBatch Reactors
Typical plant operations and equipment
Characteristics of batch operationsRaw Materials
Raw material and route selection
Large-scale charging methods and issuesTemperature Control
Large scale temperature control
Heat transfer in batch reactors
Controlling exothermic reactionsFollowing 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-downQuench & 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 modelling

Process Hazards and Safety Assessment

Common hazards in large-scale processing
Process hazard assessments and evaluations

Benefits of attending

On completion of this course you should be able 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

 

Who should attend

This course has been designed for:
  • Synthetic chemists
  • Process development chemists
  • Process engineers

in the pharmaceutical and fine chemical industries with limited pilot plant experience, who wish to learn more about the potential pitfalls of process scale-up and ways to avoid them.

What's Included

This course fee includes a comprehensive course manual, refreshments throughout the day, lunch and one course dinner. Also included in the course fee is a copy of the Pilot Plant Real Book, a unique handbook for the Chemical Process Industry, authored by Mr Fran McConville.

The course fee includes:

  • comprehensive course manual
  • coffee/tea refreshments breaks throughout each day
  • buffet lunch each day
  • course dinner on the first evening
  • course certificate
  • a copy of the Pilot Plant Real Book authored by Mr Fran McConville