23rd Jan 2018

BIOPHARMACEUTICAL-PROJECT FLOW

SHEETING & LAYOUT

AGENDA OVERVIEW

Presentation 1 Process Flow-sheeting & Equipment Layout: 10.00 to 10.30 (30 mins)

Group/Individual Exercise Block Flowsheet & Layout 45 mins

Presentation 2 Capital Cost Estimating 11.15 to 11.30 (15 mins)

Group/Individual Exercise Capital Cost estimating for flowsheet & Layout 45 mins

Presentation 3 Economic Evaluation 12.15 to 12.45 (30 mins)

INTRODUCTION & OVERVIEW

CV

▪ Gary McRobbie Chemical Engineer – Graduated in 1991

▪ Life Science Consultant with BPE www.bpe-ds.com

▪ BPE are a process led consultancy of about 25 people

▪ Predominantly worked in the Pharma & Bio Pharma Business Sector for over 25 years

▪ Worked for Pfizer for 12 years, Fermentation Technologist, Pilot Plant Supervisor, Capital Projects & Production Manager

▪ Worked for a Biotechnology equipment supplier (OEM) Pall Life Science Division for 4 years, European Sales Engineering Support Manager

▪ Last 10 years worked for various Engineering Consultancies, Kvaerner John Brown, Jacobs & PMG

▪ Clients: GSK, AstraZeneca, Novartis, BMS, Merck Serono, Pfizer

WHO ARE THE PROCESS ENGINEERING DESIGN

COMPANIES IN UKTOP TIER

Company

Fluor Engineering (Farnborough)

AMEC Foster Wheeler – Wood

Group (Reading & Manchester)

Jacobs Engineering (Manchester

& Glasgow)

Bechtel (London)

Worley Parsons ( London &

Teeside)

Company

Mott Macdonald (Croydon)

DPS (Ireland)

WSP CEL (Coventry)

Project Management Group

(Ireland & Birmingham)

MIDDLE TIER THIRD TIER

Company

Scitek (Guildford)

Manrochem (Huddersfield)

IPS- Integrated Services

(Birmingham)

BPE (Winchester)

WHO ARE THE BIO-PHARMACEUTICAL COMPANIES

Company Company

1. Johnson & Johnson 9. Abbvie

2. Pfizer 10. Bayer

3. Roche 11.Astra Zeneca*

4. Novartis 12. Amgen

5. Merck & Co 13. TEVA

6. Sanofi 14. Eli Lilly

7. GSK * 15. Bristol-Myers Squibb (BMS)

8. Gilead Sciences

Top 15 Pharma & Biotech Companies by 2016 revenue

BPE SERVICES

BPE SERVICES

PROCESS FLOW-SHEETING, FACILITY LAYOUTS AND CAPITAL COST ESTIMATING

BIOPHARMACEUTICAL TYPICAL PROCESSING STAGES

Filling & Finishing

Upstream Processing (USP)

Downstream Processing (DSP)

UPSTREAM BLOCK FLOW DIAGRAM

Cell Bank Freezer

Seed Cell Growth

& Expansion #1

Seed Cell Growth

& Expansion #2

Production

Bioreactor

Primary

Separation

Cell

Disruption

Media from

tank

Filtration &

Collection

Production

Solution to

DSP

Buffer from

tank

TYPICAL UPSTREAM PROCESS FLOW BIOREACTORS

Bioreactor 1 Bioreactor 2 Bioreactor 3

Media

ProductionMedia

Filtration

Seed Production

Media Hold

Cell Production

UPSTREAM UNIT OPERATIONS

Cell Bank

Freezer

Rotary Incubator

Wave Bag Incubator

UPSTREAM UNIT OPERATIONS – BIOREACTORS

Typical

Bioreactors

UPSTREAM UNIT OPERATIONS – BIOREACTORS

CELL CENTRIFUGATION & CELL DISRUPTION

SUPPORT VESSELS

DOWNSTREAM & FILL & FINISH BLOCK FLOW DIAGRAM

Product Capture -

Chromatography

Impurity Removal

- Chromatography

Concentrate –

TFF

(Ultrafiltration)

Virus

Filtration

Filtration

Formulation

& Filling

Product vials

Buffer from tank

Buffer from

tank

UF 1

Buffer

Production

Buffer

Filtration Buffer Hold

Chrom. USP Collection Chrom.

TYPICAL DOWNSTREAM PROCESS FLOW BIOREACTORS

CHROMATOGRAPHY

CHROMATOGRAPHY - BINDING & ELUTION

Step 1 Step 2 Step 3

CHROMATOGRAPHY

TANGENTIAL FLOW FILTRATION

FILTRATION

SUPPORT VESSELS

STERILE FILLING

FACILITY DESIGN

Process

Designs

HVAC

Systems

Facility

Layouts

…..Take all

aspects of

design into

account

FACILITY DESIGN - ADJACENCIES

PRODUCTION

FACILITY

1 - Personnel

2 - Bulk Product

4 - Liquid Waste

Kill Tanks

Visitors View

3 - Solid Waste

5 - Distribution

Media

Buffer

Equipment

Return Equip.

Fermenter Media

Live

AreaAu

ROOM LAYOUT –PRODUCTION FLOOR

EU Grade A/B

EU Grade C

EU Grade D

Technical Areas

Unclassified

CleanroomClassifications(Design Standards)

malelockerroom

femalelockerroom

male w.c.

female w.c.

autoclave

clean &sterileequipmentstore

changeroom

washroom

preparation & wrap

generalpurposearea(e.g. packing)

store

cleaner'sstore

autoclave

in-processcontrol lab.

ch. 1

ch. 2

inoculum

operators'roomharvest &

extraction

fermentation

m.a.l.

m.a.l.

ch. 1

ch. 2

m.a.l.

media & bufferpreparation

weighing

purificationroom

centrifugation/purification

+4 deg.flame-proofpurification

technical

w.i.p.store

tec

hn

ica

l

passbox

freezedryer

Finalfiltration &freezedrying

ch. 1

ch. 2

ch. 3

m.a.l.m.a.l.

main distribution corridor

ch. 1

ch. 2

m.a.l.

purification corridor

technical

250 l.fermenter

30 l.fermenter

seedfermenters

inc.

biosafetycabinet

inc.

l.a.f. unit

w.m.

operators'room

operators'room

l.a.f. unit

m.a.l.(f-p)

ch. 3

ch.4A

sh.

tec

hn

ica

l

tec

hn

ica

l

tech.

goodslift

up

stairs

lobby

wash &prep.

h.o.

a.c.

viewing corridor

l.a.f. unit

fr.

generalpurposearea(e.g. storage)

sto

re

break room

up

ch.5A

sh.

ch.4B

ch.5B

ch. 1

parts &cleanstore

technical

tech.

s

s

s

s

s

t tech.riser

tec

hn

ica

l ri

se

r

kitchen

t.

s

sh.lockers with bench

lockers with bench

lockers with bench

lockers with bench

w.c.

w.c. w.c.

w.c.

w.b. w.b.

w.b.w.b.

w.b.

w.b.

w.b.

w.b.

w.b.

w.b. w.b.

w.b.

w.b.

future link bridge

flame-proofpurification

t.m.a.l.

step

ste

p

step

step

sh.

area ofraisedceiling

t.

elec.

m.a.l.

t.

dust filters

accessstairs

t.

technical

w.b.

bench

window cleaning access only

ele

c.

fireexit

t.

fire

fire

elec.

technical

fr.

bench

s

t. bench

t.

t.

t.

biosafetycabinet

lin

e t.

tech.

t.

t. t.

floorscale

benchscale

t.

w.m.

equipmentaccesspanel

229

227

226

225

231

230

238

228

223

232233 234 237

235

239

241

242

240 243

244

249

250

248

251

245

246

247252

253

258

260

254

255

256

257

259

267

266

262

264

265

261

224

201

202

203

204

205

208

206

207

209

213

212

211

210

268

222

214215221

220

219

216218

217

236

Scale 1:100 @ A3

0 1 2 3 4 5m

City of OuluGMP Pilot Plant

PlanProductionRoom LayoutLevel +0.00m

Cleanrooms

Drawing No:440045- SK-002Issue: L

Drawn by:R.E.LinnellDate:13th Oct. 2000

ROOM LAYOUT –SERVICE FLOOR TECH SPACE

materials & equipmententrance with canopy over

personnelentrance

electricalswitchroom

electricaltranformerroom

goodslift

stairs

up

delivery &despatchdocumentation

storage areano solid wallsto be installedsub-division asrequired usingframed weld-meshscreens and doors

su

pe

rvis

or

&G

MP

do

cu

men

tati

on

m.a.l.& ch.

killtankroom

building services &process utilities plant room

store 2.

bomb shelterand store 1.

entrancelobby

circulation area

wastedilution

tank

bundwall

materialscollationarea

lobby

w.c.

receipt &despatcharea

instrumentworkshop

electricalstandbygeneratorroom

workshop

yellow hatching shows area ofhigh-level kill tank extending asa sealed zone over other rooms

securestore

water systems

shutter door

tech

. ri

ser

telecom.

solid wall at high level aroundextended kill-tank area (yellow)with support columns below wallat nominal boundary betweenstorage area and corridor.

co

rrid

or

zon

e

s

shutter door

pack

ag

eg

en

erato

r set

c.i.p./s.i.p.area

samplingarea

w.b.

sh

+0

-30

RelativePressuresin Pascals

Positive

Negative

+10

-15

-30

+0

+0

+0

+0

+0

+0

+0

+0

+0

+10

+0-10

+10

Scale 1:100 @ A3

0 1 2 3 4 5m

City of Oulu

GMP Pilot Plant

PlanBasementLevel -4.50mRelative AirPressures

Drawing No:440045- SK-014Issue: K

Drawn by:R.E.LinnellDate:4th May. 2000

ROOM SECTION

+6.90m.

+3.90m.

+0.00m.

-4.50m.

hydraulicgoodslift

liftshaft

air

in

let

ple

nu

m

malew.c.

femalew.c.

kill tank room

viewarea

fermenter room

walk-on ceiling

ch.4A

ch.5A

ch.1

technical area -services distribution

HVAC plant room

store 2

airexhausts

maincorridor

workshop store 1 & shelterm.a.l. &change

sh.

+3.00m.

utilitystation

utilitystation

raised section approx. 6.1 x 1.8m.

+4.20m.

delivery &despatchdocumentation

services zone

fire wall

contained pipework zone

w.c. w.c.shower shower

bund wall

Scale 1:100 @ A3

0 1 2 3 4 5m

City of OuluGMP Pilot Plant

SchematicSection A - A

Drawing No:440045- SK- 91Issue F

Drawn by:R.E.LinnellDate:29th Jun. 2000

HVAC & MECHANICAL SERVICES OVERVIEW

HVAC & PLANT ROOM

FACILITY GMP CLASSIFICATION

Air cleanliness

Considering Annex 14, Annex 1 and existing facility classification; EU GMP grade C / ISO 8 / Class 100,000 is considered appropriate.

Pressure regime

At this stage, 15Pa minimum DP is considered necessary cascading from product manufacturing areas through critical barriers to the background CNC corridor. Please refer to pressure regime drawing (709-GA-100).

Room temperature & relative humidity

This is not considered a GMP requirement – only provided for comfort. Any product or GMP critical temperature or relative humidity will be provided by the equipment package and suitably integrated into the room.

Viable Particle control

Surface and people cleanliness, microbial controls are deemed as current procedures

Environmental Monitoring System

We understand CMR provide a international cGMP compliant side-wide environmental monitoring system which is proposed to be utilised on the new manufacturing facility.

HVAC CLASSIFICATION OF AREAS

HVAC AHU ZONING

GROUP /INDIVIDUAL EXERCISE

Develop a Process Flow Block and Pictorial Flow for new scale up project.

Guess equipment dimensions. ASK

Develop a simple facility layout that includes equipment and their associated

room layout with some preliminary dimensions.

Think about what utilities and services may be required for both HVAC &

Process. Clue Water, Steam etc. Show on facility layout.