biotech. facility design
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Biotech Manufacturing Facility DesignMichael Chan
PQC Consulting, Inc., USA
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An Integrated PlantBulk API productionFill & FinishPrimary & Secondary PackagingQC LabsCentral Utilities Plant
Warehousing & DispensingQA Personnel Administration
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ISO 14644
To convert from ISO classification to Federal 209 D, divide the particulate concentration by 35.2 to convertfrom cubic meter to cubic feet. Hence, ISO Class 5 is equivalent to 209 D Class 100.
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Rule of Thumb for HVAC Design Criteria
ISO Class Monitoring &Controls
Air Velocity attable level in
feet per minute
Air ChangeRate per hour
HEPACoverage as% of Ceiling
5 Very Strict 70 90 150 400 100
6 Medium 25 40 60 100 33 40
7 Medium 10 15 25 40 10 15
8 Adequate 3 5 10 15 5 - 10
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DSP SuiteAir Flow Diagram
Buffer PrepClass 8
(--)
Material A/L
FillingClass 6
(++)
ComponentPrep
Class 7(+)
ProcessingClass 8
(+)
Personnel A/L
Tank StorageClass 8
(+)
FiltrationClass 7
(+)
A/L
A/L
Corridor Class 8 (-)
Dirty Corridor
Tank CleaningClass 8
(--)
A/L
Filling lineClass 5
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DSP SuiteMaterial Flow Diagram
Buffer Prep
Material A/L
Filling
ComponentPrep
Processing
Personnel A/L
Tank Storage
Filtration
A/L
A/L
Corridor
Dirty Corridor
Tank Cleaning
A/L
CleanDirty
Filling line
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DSP SuitePersonnel Flow Diagram
Buffer Prep
Material A/L
Filling
ComponentPrep
Processing
Personnel A/L
Tank Storage
Filtration
A/L
A/L
Corridor
Dirty Corridor
Tank Cleaning
A/L
CleanDirty
Filling line
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Functions of Biotech Manufacturing PlantCore Processing
Upstream Processing Media prep Seed reactors Fermentation/Recovery, centrifugation, homogenization Tank storage & cleaning Unclassified to Class 100,000
Downstream Processing Buffer prep Buffer storage Purification, chromatography systems, microfiltration, ultrafiltration Equipment storage, cleaning Class 100,000 to Class 10,000
Filling & Filtration Component prep: wash, sterilization
Vials, stoppers & seals Lyophilization Filling & Inspection Class 10,000 to Class 100
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Support Functions Utilities
Central vs. dedicated utities WFI & USP Purified water storage Skid based systems: WFI, RO, Clean steam, CIP, SIP, columns, UF/DF Dirty utilities: steam, potable water, compressed air, nitrogen Media and buffer storage in unclassified areas Interstitial space
Administration Management & Staff Batch records, SOPs, Validation, Maintenance, etc. storage
QA/QC Management & Staff Samples Lab space
Warehousing/Raw Material Incoming, quarantine, released products Sampling and dispensing
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Design Considerations Transfer Panels
Minimize valving and direct tank-to-tank piping Use non-classified areas for media and buffer holding tanks Gravity Feed
Requires use of elevators for material and personnel transfer Minimize pressurization transfers
Interstitial space & catwalk for maintenance access HEPA filter accessibility from interstitial space Sanitary piping
Sloped and minimize deadlegs Ensure maintenance accessibility for valving and instrumentation
Reduce visitor intrusions by building in viewing windows
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Project PhasesScope Definition
Design Development
Detailed Design
Construction
Start-up
Validation
Sets the Project s Founda t ion Establish Project Scope & DriversDefine Capacity & Through-put Set Design CriteriaPrepare Budget Form Project TeamDefine roles and responsibilities
Agree upon Project Schedule
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Project Drivers, Scope & Objectives Define the Project s Drivers
Why is the project needed? What happens if the project is not implemented? Increasing product pipeline Higher market demand for product Redundancy/Back-up capacity
Set Project Limits and Scope Products to be manufactured in the facility Clinical vs. commercial
Compliance with US, EU, Japan, Middle-East regulatory requirements Included functions: Manufacturing, QA, QC, Fill & Finish, Packaging, Administration, etc
What will the Project achieve at the end?
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Key Elements of Design Development Production capacity must be tied to marketing or product development
requirements Expansion capabilities Redundancy requirements
Multi-product vs. single product train Operating assumptions (shifts) Product and personnel flows Centralized warehousing/dispensing vs. localized Methods for material transfers Regulatory Compliance (U.S., EMEA, e Local and national building code review Process and unit ops descriptions Utility systems Environmental constraints Level of automation Equipment list and identify long lead time items Incorporation of PAT
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Case Study Existing Facility
Microbial fermentation Scale-up reactors 50L, 200L and 800L Cell harvest and protein recovery in fermentation hall using portable media
tanks Separate purification suite using portable systems/skids 8,000 s.f. facility
Expansion Additional 10,000 s.f. Use 800L as scale-up bioreactor New 2,500L media prep tanks New 2,500L convertible microbial/cell culture bioreactor New dedicated cell harvest and recovery suite with fermentation broth hold
tanks New buffer prep suite with fixed tanks New purification suite with 3 skid stations
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Lessons Learned Expansion did not consider large scale material handling Too much piping in too little space resulting in difficult maintenance Facility contamination due to personnel crossover from under
construction areas to existing facility Should have had better personnel segregation
Plan for utility tie-ins well in advance Involve current plant personnel early in design phase and integrate
into project team Integrate new plant SOP s and validation documentation into existing
system Incorporate over-arching change control for new plant
All validations must be completed and QA approved
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