Continuous Manufacturing and Crystallisation

(CMAC)

Workshop

2nd November 2010

Format of the CMAC WorkshopPart 1: Presentation

• Vision / Rationale for the CMAC Centre and Overview of Research Themes, Mr Ian Laird, University of Strathclyde/NiTech Solutions (Industrial Director of proposed EPSRC Centre in Innovative Manufacturing)

• Question / Answer session with members of the academic team present:

- Professor David Littlejohn, Chemistry University of Strathclyde

- Dr Jan Sefcik, Mechanical Engineering University of Strathclyde

- Professor Xiong-Wei Ni, Chemical Engineering, Heriot Watt University

- Dr Graeme White, Chemical Engineering, Heriot Watt University

- Professor Lee Cronin, Chemistry, University of Glasgow

Format of the CMAC Workshop

Part 2: Breakout Sessions

• Importance of Continuous Manufacturing and Opportunities for Particle Product development - focus on product differentiation rather than process development (facilitated by Craig Johnston, Britest/Fujifilm)

• Who, within Scotland, UK and beyond may be able to contribute to/support/benefit from the Centre (facilitated by Ian Laird, University of Strathclyde/NiTech Solutions)

• Potential TSB Funding opportunities related to CMAC (facilitated by Linda Wallace, University of Strathclyde).

• Feedback from the Breakout Sessions

Continuous Manufacturing and Crystallisation

Vision & Rationale

Ian Laird

Pharma / Chemical Industryis in a lot of

pain

Sustainability

Evolution of Manufacturing

Technology for Chemicals Industry

� Little has changed in 450 years

� The stirred tank reactor is the “normal” approach for manufacture

� Particular challenges around the scale-up of processes

� Expensive, poor control over quality

c.1556 1956 2010

New Paradigm

– Continuous

Manufacturing� Adoption of Lean Manufacturing Principles

� Avoid challenges of large batch by steady continuous process

� Growing levels of interest

� 7 of top 10 global pharma companies and many speciality and

fine chemical companies engaged in this

� New research activity (e.g. Novartis-MIT)

� Benefits include:

� Lower costs – capex, operating costs, working capital

� Greater control over product quality (more predictable scale-up)

� Sustainability – less waste, “greener chemistry”, lower CO2

footprint

� Greater responsiveness – speed to market, adding capacity

� But, no complete solution exists…

CMAC: Centre of Excellence in Continuous

Manufacturing & Crystallisation

Delivered through:� Cross-sectoral and cross-functional

collaborative partnership

� leading academic institutions and major industrial companies.

� Leveraging collective knowledge across the supply chain

� Collaborative funding model to create exceptional business performance & growth

Public Sector

Academia

Industry

The Vision:� World renowned research facility for fundamental and applied research

in continuous manufacturing & crystallisation.

� Driven by Industrial Needs and demand

� Rapid “technology pipeline” from concept -> demonstration –> exploitation.

An Unrealistic Dream…

Or Within Reach?

NiTech Reactor volume reduced

by 99.6% against traditional

approach

The world’s largest patent-

protected continuous pharma API

plant is at Genzyme, Haverhill

Creating Rapid Technology Access

1

2

3

4

5

6

7

8

9

TRL

Technology

Assessment

& Proving

Pre-

Production

Production

Implementation

UniversityResearch

R & D Industrial Exploitation

Research

CMAC

Development

Deployment

Demonstration

Proven Value Delivery

Experience

Advanced Forming

Research Centre� Industrial demand driven applied

innovation

• Boeing, Rolls Royce, Airbus,

Aubert Duval + others

• Additional involvement from

supply chain and partners

� Activity underpinned by academic

excellence

� £6m of private sector investment

leveraging additional £30m

� Collaboration / Funding / IP

frameworks

What will it do?

– Direct support:

• Member plant and product support

– Generic programme:

• Tier 1 membership contributes to the generic programme, based on Tier 1 member requirements.

• Tier 1 members have free right of use for IP Generated.

– Member specific programmes:

• Tier 1 members can also undertake individual activity

• IP generated is owned by the sponsoring company.

– Technology Fore-sighting:• Future research, disparate markets.

Deliver solutions to enhance

customer’s manufacturing processes.

CMAC Board

CMAC

Leadership Team

AFRC Team

Objectives / Tasks /

Challenges / Priorities

Industry driven

Chair Industry

CMAC

Technical

Board

Research Agenda / Technical Focus

Project proposals / IP Identification

Ideas / Funding Opportunities

(DTI, EU,EPSRC) etc. All sponsoring

Universities

CMAC Key Principles

Governance Model

CMAC Team

Theme Leaders

Research Associates

New post-docs & PhD’s

Day to day management

of centre, research

and University activities.

What might the future look like?

Driven to Meet Needs

� End-user engagement and participation

� Strong alignment of activity

� Proposals created to address requirements

10 Areas of Focus

What is in this for you, your

clients, someone you know?

How can you help?

Manufacturing Operations

Supply Chain

• Manufacturing operations and supply chain configuration

• Management control systems

• Lean / 6Sigma

• Change Management

• Learning from experiences of other industries

• Stimulation of new technologies and solutions

10 Areas of Focus

Influencing Product Design

2

Understanding of kinetics and process,

design of continuous systems

Self-assembly control of particles

including heterogeneous

Provision of new and optimised

materials into the pipeline • Coupling of novel chemistry /

nanomaterial assembly with continuous

crystallisation process

• Backward integration and use of

continuous crystallisation processes to

select better or novel synthetic

pathways to deliver materials into the

manufacturing pipeline

• Focus on synthesis and nanomaterial

assembly (pharmaceutical and

electronic material areas targeted for

proof of principle)

Graphical Summary of two

‘synthetic’ Approaches

5

Development of these continuous systems offers huge flexibility in

providing new or optimised materials for the continuous process

pipeline.

Synthesis will offer access to new materials not otherwise

available.

Self-assembly offers nanoscale control of particles, including

control of architecture and composition.

Prof Colin Pulham

Continuous Manufacture of Robust and New Solid Materials

Prof Xiong-Wei Ni

Dr Graeme White

Prof Chris Rielly

Prof Zoltan Nagy

Understanding Oscillatory

Baffled Continuous

Crystallisation

Direct Nucleation and Model

Predictive Control for

Continuous Crystallisation

direct nucleation control (DNC)

model predictive control (MPC)

Understanding

optimisation

Prediction

demonstration

Moving from batch to continuous..

...brings new demands for

in situ process analysis

New Solutions Require New

Technologies

• use different measurement techniques

– multi-point measurement techniques – smaller, less

expensive, but high information content

• combine different techniques for better process

understanding and modelling

• control strategies for more consistent

manufacturing – tuning the process

• integration of more unit processes in a continuous

supply chain

• demonstration of technology

• access customers

Better Measurement,

Understanding, Control & Prediction

Questions?

Engagement in discussion