Consultancy.

Project Delivery.

Innovation.

Case Study: API Recovery Process

Process Design leads to £10m/year savings

Client: Multinational Pharmaceutical Manufacturer

Who are we?

Process engineering consultancy

Specialising in advanced modelling techniques, to give answers that

are more accurate, reliable and robust

Decades of process and mechanical engineering experience

Combine cutting edge simulation with real world understanding, to

provide you with solutions that are effective and practical.

Experience in Pharmaceutical / Fine Chemicals

Page 2

Project Background

FDA Approved Process

Manufacture of valuable API, recovered through filter dryer

10% of product lost as 0.7% solution in aqueous mother liquor,

representing ~£15m/year

Lab scale trials had demonstrated 90% recovery of this when extracted

with acidified MTBE in a stirred batch vessel

Caustic added to MTBE solution, API forms the soluble sodium salt in

the aqueous phase in concentrated form.

MTBE removed by batch vacuum distillation

Calcium added to aqueous phase to precipitate out the API

API re-filtered and spent mother liquor sent for further effluent treatment

Page 3

Our Responsibilities

Work within constraints fixed by pilot trials and FDA application and

three possible locations on site

Complete survey and feasibility to determine best location, that:

Minimises cycle time, does not restrict main production of API

Minimises capital cost

Can be sufficiently automated

Will not result in more solvent emissions from the site

Write up feasibility work and produce flow diagram of proposed option

Develop Front End Design

Develop Detailed Design

Page 4

Final Process Flow Diagram

Page 5

+5°C HTF

Vent

Condenser

E6-3010

VOC

Abatement

FIQ

Pure

Water

+5°C HTF

Vent

Condenser

E6-0984

VOC

Abatement

GN2

FIQ

Pure

Water

E6-0700

Feed

Vessel10m3

1500, 1600 & 2000

Mother Liquors

Salt Soln to Heel Recovery

Retreat

Material or

NaCL

E6-3003

GN2

GN2

GN2

GN2

PRODUCT

+5°C HTF

Condenser

1M HCl

YI

3rd Floor

1st Floor

Ground Floor

2rd Floor

E6-0500E6-0800

E6-0600

E6-0400

YI

Dedicated

Filter Dryer

Calcium Chloride

(Ex-E6-1829)

MTBE Solvent

(ex Bulk)

+5°C HTF +5°C HTF

Vent

Condenser

Vent

Condenser

FIQ

1M

HCl

0.25M

NaOH

Decant

Decant

pH

pH

+5°C HTFDistillation

Condenser

E6-3003 (Spent MTBE)

4m3

E6-3003 (Waste

Distillate)

FIQ

Pure Water

10m3

10m310m3

6.3m3

E6-1320

E6-1300

SOLID PRODUCT

to Matcon Bins

Precipitator

E6-3101 Waste Tank

(Grand Mother Liquors)

Dedicated

Filtrate

Receiver

Aqueous

Receiver

Extract

Receiver

Extraction

Vessel

Vacuum

Distillation

10m3

VOC

Abatement

+5°C HTF

-20°C HTF

Condenser

Condenser

E6-3003

E6-3005

3005

E6-3003/5

E6-0200

E6-3005

E6-0207

E6-0204

E6-0201

E6-0507

0.25M

NaOH

Pures Charging

Booth

E6-0420

E6-0520E6-0505

Organic

Aqueous

Waste

E6-3001

E6-0208

4" S

elf V

en

t - Lin

ed

6" S

elf V

en

t - Lin

ed

3" S

elf V

en

t - Lin

ed

E6-0613

E6-0511

Venting

Manifold

E6 – 0825

(coarse filtration)

SP

E6

-02

05

SP

HCC Pump

E6-0203

Vent

E6-0206

+5°C HTF

Vent

E6-0605 E6-0405

E6 – 3505

(fine filtration)

E6-0211

Vac Pump

E6-0980

VOC

Abatement

+5°C HTF

Vent

Condenser

VOC

Abatement

E6-0512

VOC

Abatement

E6-1200

Precipitator

Filters 1520,

1620, 2020

Glove

Bag

E6-0982

(Ex E6-0613)

Backventing Line

E6-3003

GN2

SI-01

SI-02

SI-03

FCV

Waste

Receiver

INVENTORY 11

INVENTORY 08

INVENTORY 09

INVENTORY 10

INVENTORY 07

INVENTORY 02

INVENTORY 01 INVENTORY 04

INV

EN

TO

RY

03

INV

EN

TO

RY

05

INV

EN

TO

RY

06

Including all

Services/

Utilities &

Relief Streams

INVENTORY 12

INVENTORY 13

MTBE

Storage F120

& Transfer

Line to E6

E6-0713E6-0413

1st Floor

Ground Floor

2rd Floor

E6-0202

(Ex E6-0511)

Part of Inventory 12

Inside E6

Cycle Time Evaluation – Software Tools

Page 6

Using Aspentech’s Batch Plus Simulation Software to:

Develop process recipe and run as a script

Quickly identifies pinch points and conflicts

Optimise process step timings and use as basis for sizing equipment

Obtain outline heat and mass balance and utility consumptions

Support the design from concept to commissioning

Develop first draft Standard Operating Procedures

Develop OQ Protocols

Process Design Activities – Part 1

Process changes on P&IDs

HAZOP

Checking suitability of existing equipment (e.g. pumps, lines)

New line sizing (pumped and gravity) for new plant configuration

New equipment specifications (e.g. vessel, agitator, heat exchangers)

Full materials of construction review, particularly as strong acids used

Consideration of MTBE vapours when moving liquids between vessels,

quantifying simultaneous vapour losses to assess impact on CATOX.

Specification of high efficiency knock-back vent condensers

Page 7

Process Design Activities – Part 2

Full utility assessment, particularly on chiller system, to understand

instantaneous demands and impact on other building users.

Balancing heat transfer fluid systems to route to new locations.

Assessment using network flow software such as AFT Arrow/Fathom

Two phase reacting relief studies for vessels and jackets

Development of IQ/OQ protocols and briefing of production staff on new

process design

Overseeing mechanical design to ensure that process requirements are

met

Page 8

Outcomes

Predicted cycle time and product recovery proved on commissioning

Design made the best use of existing equipment and maximised gravity

transfers to avoid purchase of additional pumps

Project budget and timescales met

Minimal required changes at commissioning

Client reported years of trouble free operation since commissioning

Page 9

Summary

Led FEED and oversaw Detailed Design to deliver process providing

client with ~£10m/ year savings

Used a combination of simulation expertise and design experience to

minimise capital costs (including re-use of existing equipment) and

optimise operations

Fully evaluated all the production risks with sharing the facility, including

ease of construction, risk of cross contamination and automating needs

Provided a full design package with supporting process calculations and

documentation, including two-phase reacting relief

Process was implemented with minimal start-up changes, and predicted

cycle time was validated

Page 10

Summary

Page 11

Consultancy.

Project Delivery.

Innovation.

Please get in touch to find out how we can help your

business today.

E: enquiries@flexprocess.co.uk W: flexprocess.co.uk

T: +44 1454 629 689