primary continuous processing retrofit

PRIMARY CONTINUOUS PROCESS UPGRADE

Shamai Cylich, Arcadis, Sr. Project ManagerScott Cheeseman, GSK, Sr. Process EngineerSteve Walter Hargrove Life Sciences, Process Technology Leader

PRESENTATION OUTLINE• Scott

Process Design Development

• Steve

Facility Design Development

• Shamai

Project Management

Closing

PROJECT BACKGROUND

• Process development trends – exploring flow chemistry by first intent

• Benefits of continuous processing• Bridge to commercial facilities

• Existing/limited facilities footprint – for batch equipment• Single known user requirement: Agile flexibility!• Designing to a vision

Project Drivers in Pilot Plant Environment

Known Challenges

PROCESS DESIGN DEVELOPMENT

• Smaller facilities footprint for equal capacity• Lower energy requirements for heat transfer• Lower solvent requirements• Improved control of energetic reactions• EHS improvements – smaller quantities at any given time

All understood – just no Pilot Plant capability

Expected Benefits – The Basics


BATCH CONTINUOUS


Safety

Flammables

Containment

Personal Protection

Process Safety

Flexibility

Unit Operations

Equipment Train

Breakdown/ Turn‐around

Access to Utilities

CONSIDERATIONS


• Flow chemistry equipment is available• Examples of lab set‐ups are common• Examples of large commercial set‐ups are common• Pilot Plant Space not well defined….at least for this project

• Agile Flexibility

Early Lessons Learned


• Delivery of raw materials, collection of product and waste solutions

• Utility needs• Typical safety needs• Typical footprint of equipment – is a typical space acceptable for all equipment (modular?)

• Flexible automation

• Technical transfer requirements

Understand the (Every) Process


Models

PROCESS DESIGN DEVELOPMENTModels

UTILITY REQUIREMENTS

PHYSICAL LIMITATIONS

BLAST CONSTRAINTS

FLEXIBLE DESIGN

PACKAGED SYSTEMS

FACILITY DESIGN DEVELOPMENT

• EXISTING• Breathing Air• Process Water• Nitrogen 10#• Nitrogen 85#• Plant Steam • Condensate• HTF S/R• Process Vent• Hydraulic Fluid• WFO

UTILITY REQUIREMENTS

Adjacent Processes – In

Use

Shut downs &Planning across multiple projects simultaneous

Survey Confirmation

Min Qualified Systems PID Field

ELIM

INAT

ED

FACILITY DESIGN DEVELOPMENTUTILITY REQUIREMENTS

BATCH CONTINUOUS

Plant Steam & Condensate

Hydraulic Sys (Agitators)

Existing HTF Sys: Syltherm‐25C to 160C

Required Multiple

Simultaneous Differing Temps

Limited Temp Range

Single Source

FACILITY DESIGN DEVELOPMENTUTILITY REQUIREMENTS

BATCH CONTINUOUS

• Limited HE Area• Scale Up‐ Space• Larger Volume Rinse / Chase

• Process Water

• Surface Area to Volume Ratio Increase

• Scale Up In Place• Min Volume Rinse / Chase

FACILITY DESIGN DEVELOPMENTPHYSICAL CONSTRAINTS

32 Process Conn HT Kit (3x)

Duct, Data, Drain,

Sprinkler


127.5” To Underside

104.5” Process Plant

23” of Clearance

‐ Exhaust Duct‐ Sprinkler‐Wire Duct‐ HTF S/R‐ Cooling Water‐ N10, N85, &N500‐ Vent‐ CA


Valve & Instr Access

Electrical Clearances

Mechanical Access


• BEFOREPHYSICAL CONSTRAINTS

~16’ X 16’ Area:• 2 – 50 & 2 – 200

Gallon GL Rx• 2 – Hydraulic Ag• Jkt Circulation

Pumps• Jkt HX• Condenser

4 Reactor Bays – Thru

Floor

Delta V MCP


• AFTERPHYSICAL CONSTRAINTS

~16’ X 16’ Area:• 8 Vessels – upto

1600L (350 G)• Supply Materials

Product and Waste Collection

• 4 – Utility Panels• 4 – Filter Stations

and Automated Valve Panels w/ 4 future spaces avail

• LEVs


• Analysis Provided:• Wall • Floors • Relief Panels

BLAST ANALYSIS

Blast Hazard Analysis and Preliminary Dynamic Structural Analysis

Quantify Any Structural or Near Yield Hazards

Adequate for Intended Operations

Doors

EXCEPT:

Unable to Confirm

Existing Door Design


• Enclosure Components not Electrically Classified

• Raw Material / Product Staged in Adjacent Area

ADDITIONAL SAFETY /HAZARD

Hazard Area Classification

HAC

Vessel Design• Tipping Calcs• Not Plausible

Mechanical Design

• LEL Detection• Secondary Containment

• Max Door Opening


• FLEXIBILITY• Utility Panels• Transfer Panels• Hose Connections/Management

• 360 Access for entire plant

• CONSIDERATIONS• Consistent Design• Utilize similar components

• Organization

FLEXIBLE DESIGN

Adapt to Future Needs of Continuous Processing

FACILITY DESIGN DEVELOPMENTFLEXIBLE DESIGN


• Panel Design• Compact • Single Source• Experience

• Benefits• Consistency• Standardized Approach• Design portion completed for future install

PACKAGED SYSTEMS


• Transfer Hoses & Panels• Compact • Minimum Floor Space

PACKAGED SYSTEMS


• Hose • Location • Visual • Separated

HOSE MANAGEMENT

PROJECT MANAGEMENT

• PM 101 – Deliver project on time, in budget, and meeting all functional requirements

• 1st of its kind – didn't really know what we had or how best to utilize

• No precedent for pilot plant design…many design evolutions

• Schedule – very aggressive…. at first 6‐9 months• As the team grasped the larger potential we realized it was better to get it right than to rush…more budget and 2 years to implement.

SCHEDULE

PROJECT MANAGEMENT

• Performing renovations in an operating plant –windows for shutdowns, dust control, etc.

• Took out the batch reactors, pulled up acid brick floor, closed floor openings laid new ESD epoxy flooring.

• Change paradigm of space utilization – (re)connect accessibility and increased visibility for the operators.

RETROFIT CONCERNS

PROJECT MANAGEMENTMockups

Mock‐up for VIP Tour

Rough Scale Mock‐up

Final True‐Scale Mock‐up

PROJECT MANAGEMENTRisk Management

HAZOP

Concept Design, Design Complete and Construction

Limited to CP, Utility and

Infrastructure

PRA’s specific to chemistry

EHS, Auto, Proc Eng, Ops, PM

226 Action Items

• Established VWP early• Developed Project Master Validation Plan early start but took a while to complete.

• Challenges:• URS was purposely not defined at beginning of project….rather it evolved as the team grasped the capabilities of the technology and how to apply it.

• Automation – Delta V was a GMP qualified system, project was able to segregate the work‐in‐progress from the existing qualified system.

PROJECT MANAGEMENTCQV

PROJECT MANAGEMENTCQV

VALIDATION PLAN

DELTA V ‐ CC (QA)

SFAT PROCONE

HFAT ACI

Utilities & Infrastructure Demolition / Construction (GEP & GMP)

Facility & Utility Commissioning (GEP)

FCPP FAT Zeton

Shipping

Install Process Plant GSK UP

Loop Checks QA

CalibrattionQA

Process Commissioning (Pre‐GMP) Su

bstantialCom

pletion for N

ON‐GMP

Ope

ratio

n 15

‐Aug

‐2016

IQ/OQ ‐ Software & Hardware Finalize &

Execute (QA)

Shipping

• Key component of the Commissioning effort• HFAT – new control panels ‐ locally• SFAT – software configuration and graphics ‐ locally • Process FAT – shipped control panel and Delta V server with the program files to Mfr facility.

• We learned a lot during the 2 week FAT about what we had purchased!!

FATs

PROJECT MANAGEMENT

FAT ‐ Process

PROJECT MANAGEMENT

Continuous Plant Electrical/Control Panels Smoke testing

Installation

PROJECT MANAGEMENT

Skid Arrived!!Just fit through the roll door

• Site Commissioning – essentially a repeat of the FAT…learn by repetition!

• The team was getting very proficient at using their new toy!

• Current Status – Cx complete – ready for development work.

• Qualification will be executed once a specific GMP campaign is scheduled.

Installation

PROJECT MANAGEMENT

Installation ‐ Before

PROJECT MANAGEMENT

2nd Floor 1st Floor

Installation ‐ After

PROJECT MANAGEMENT

2nd Floor – North Wall 1st Floor