Multiproduct
Production
A Case Study
Mark White
DPS Engineering
22nd May, 2014
Overview
▶
Current Trends
▶
Project Brief & Design Evolution
▶
Design Requirements
▶
Ongoing & Future Development
Current Industry Trends
Rebalancing of Manufacturing Assets
•
•
Large Scale API hardest hit
Evolution & Repurposing of Manufacturing Sites
Fewer ‘Blockbuster’ drugs in Pipeline
•
•
Focus on Speciality Pharma / Patient Needs e.g. Oncology
Smaller Volumes / Higher Potency Drugs (‘Nichebusters’ )
Need to get to Market Sooner
•
•
Reduced Development Time
Faster Production of Kilo Quantities
Lab Scale to Batch Scale
•
•
Scale Up Efficiency
Reduced Turnaround Times
Small Scale Project Drivers
▶
Small Volume “Niche” Drug Products
▶
Fast & Flexible Production of (Early Phase) Pharma Materials
▶
Sustainable Production Technology
▶
Reduced Capital Investment for NPI (New Product Introductions)
▶
Negate Bulk API Plant Operating at Inefficient Volumes
DPS Project Brief
•
Reactor Capacity
not suitable for low
volumes
•
Separate
Production
‘Suites’
•
Product
introductions
slow & costly
•
Manufacturing
& Isolation
Capability
•
Make best use
of existing real
estate
•
European Initiative
•
Futureproof
Investment
•
Reuse existing
utility services
Scope Evolution
Client Led Concept
Front End Study
Detailed Design
• Concept Study (Focus on
Feasibility & OOM Cost)
• Focus on Layout &
Ancillary Requirements
• Interactive Cross Functional
Team
• Challenge Equipment
Train
• Develop 10% Cost
Estimate (Project Budget)
• Emphasis on 3D
(30% / 60% / 90%) Reviews
• Client Co-location and
Interaction
• Detailed Design of Long
Lead Equipment in Parallel
• ‘Fast Track’ Design Process
Equipment Train Identified
Key Constraints
€
Approved Budget
Extensive
‘Value Engineering’
Throughout
Project Schedule
• OOM at Concept Stage to
allow Project Funding
Request
• Use of Repurpose
Equipment & Infrastructure
• Estimated 18 months Project
Duration (standard
approach)
• 10% at FES Stage (Higher
than funding approval)
• Regular Cost Trending &
Design Change
Management
• Market Driven Requirement
12 months (fast track)
Design Development
Design Development
Highly Interactive
ISO Output from ‘Issue
for Hazop’ Stage
Pre-IFC and Post-IFC
Changes Developed
• Significant P&ID & design
document reviews
• Risk acceptance by client
• Approved (& tracked) or
rejected
• 3D model used extensively
for formal reviews
• Bulk MTO generated at
frequent intervals
• Traceability throughout the
project lifecycle
Design Requirements
& Key Functionality
Equipment Scope v. Process Fit
Multiple
Process Fit
Scenarios
Evaluated &
Challenged
Allow Use of
‘Flow Skids’
(Footprint &
Hook-Up)
Established
at Concept Stage
(Primary Design
Foundation)
Hydrogenation
Sizing Reevaluated
Scope
5-25kg
Suite 1
Suite 2
4 x Reactors
(2 x 400 / 2 x 600 litre)
3 x Reactors
(100 / 160 / 250 litre)
•
•
1 x Head Tank, Drum
& Reagent Booth
•
2 x Head Tanks, Drum &
Reagent Booth
•
Contained Tray Dryer
& Dual Tray Dryer
•
Peeler Centrifuge (22
litre)
•
2 x Receivers (400
litre)
•
Agitated Filter Dryer
(0.3m2)
•
HS Wet Mill, 2 x
Receivers (1,000 litre)
•
Hydrogenation
•
1 x Reactor (400 litre)
•
Catalyst Filter
MOC Selection
Agreed list of Solvents &
Product Materials
Specific Hastelloy
/ Hastelloy Free
Reactors per Train
‘Balance’ of Exotic
Materials (GLCS,
Hastelloy ‘C’,
Tantalum, Stainless)
Layout Development via 3D Interactive Reviews
Central Technical Space Servicing
Two Separate Suites (c/w Airlocks)
Layout /
Segregation
Common Staging & Dispensing Area
Hydrogenation Area Separate
(shared services)
Adjacent Office & Support Areas
Interconnectivity
Transfer
Manifolds
Significant use
of Flexible
Hoses
Mobile Head
Tanks &
Receiver
Vessels
Flow Skid
Utility Plates
Automation Strategy
Existing
Delta-V (No
Recipes)
Reduced
Automation
Emphasis on
Manual
Operation,
Operator OIT’s
Hardware /
Software
Interlocks
defined during
PHA review
Detailed
approved URS
documents for
all systems
Containment
• General Operation to OEB3 (100-10 µg / m³)
• Charging of OEB4 via Specific Technology (10-1 µg / m³)
⁻ Use of Split Valves
• Enabled for OEB5 Category Material (<1 µg / m³)
⁻ Flexible ‘Bags’
⁻ Isolation Glove-boxes
Cleaning
• Cleaning Philosophy Document Developed
• Simple Approach
⁻ Recirculation via Process Pipework
⁻ Spray-balls Integrated where necessary
⁻ Vessels can be cleaned in isolation
• Flex Hoses Cleaned-In-Place
Ancillary Services
• Weak Effluent for General Waste
Streams
• Use of Existing DFB coupled with
New Glovebox
• Strong Effluent for Process Waste
• Common Access, Egress & Staging
Area
• Repurpose Tanks Employed
• New Airlock Included for Pressure
Segregation
• HEPA Filtered Supply to
Dispensary Make-Up
• Liquid Ring System (Process)
• Dry Running (Isolation)
• Repurpose Vacuum System
for Contained Tray Dryer
• 50/50 Glycol System c/w
Tempered Condenser Loops
• -20 to +150°C Range
• Specific Vessel Enabled for Low
(-80°C) Temperature Operation
• Separate Acid & Base
- tied into existing Abatement Device
• Repurposed Tanks Employed
• Direct to Atmosphere for H2 Evolving / Hydrogenation
Reactors
Ongoing & Future Development
Flow Skid
Hydrogenation
Area
(CM phase)
•
Design complete
& Reviewed
•
Installation & CM
Support in
Progress
(Re-Design & CM)
•
Design
Development
•
Confirm Process Fit
& Design Basis
‘Phase II’
development
(‘Future’)
Key Project Statistics
2,100
Piping
Isometrics
2,910 L
Total
Reactor
67 No.
P&IDs
29
Separate
Systems
7,500 m
Pipework
Lessons Learned
Engage with All Stakeholders
from Outset
⁻ Include in Early Reviews & 3D
Interactions
⁻ Solicit Opinions
Value Engineer From the Outset
⁻ Agree Scope Early – Late Design
Changes are Major Impacts
⁻ Track All Changes
Optimise trade-off between ‘Best’
Layout v. Minimum Hold-Up
⁻ Vertical Stack-up Preferred
⁻ Never Base Design on Large Scale
API Equipment
Never Underestimate Piping or
Instrumentation Design
⁻ Maintenance and Operator
Access Must be Incorporated
⁻ Only Vessels are Small Scale!
Flexible Approach
Project Success
Integrated Team
www.dpseng.com