Fundamentals of

Biopharmaceutical
Facility Design
INTAS BIOPHARMACEUTICALS LIMITED

S. BALLAL & M. KODILKAR

Dec 29, 2010

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 Program
 Introduction
 Key Design Parameters
 Emerging Trends
 Design Process
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 Introduction
 Traditional: Single
product facilities
 1990’s: Multi-
product facilities
introduced
 GMP evolves to
permit multi-
product operations
with shared
equipment
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 Key Design Parameters
 Process Flows / Unit Operations
 Process Volumes
 Biosafety
 Viral Segregation
 Multi-product V/s Single Product
 Regulatory Requirements
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 Process Flows
 “Biopharma facilities are built around the process”
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 Process Flows
 Segregation
 Inoculum prep
 Centrifugation: noisy, aerosol generating, difficult to
clean
 Pre viral & post viral steps in DSP
 Column packing areas: open, manual operations
 Solvent use areas: flame-proof zone
 Product changeovers: Segregation in overlapping
batches
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 Process Volumes
 Large (~ >1500L)  Small
 Stationary systems
 Hard piped
 CIP/SIP
 Centralized CIP
 Long pipe runs
 Multistoried units
 Mix of stationary, mobile
 CIP hardpiping preferred
 COP/SOP possible
 Multiple CIP units
 Large MALs, corridors
 Space for clean staging

 CNC spaces for less critical operations, closed operations

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 Biosafety
 BL1 preferred.
 Exponential rise in capital cost with higher Biosafety
levels
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 Viral Segregation
 Detection of potentially harmful viruses in DS (Porcine
parvovirus in Factor VIII)
 Principle concern: “Segregation of post-viral material from
pre-viral”.
 Extended to segregation in area, airlocks, washing.
 Separate AHUs and washing areas
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 Multi Product /Single
product
 Multi Product Facility
 Need flexibility for
accommodating processes
 Equipment more flexible in
operating ranges
 Utilities oversized
 Pre-determined, multi-
directional transfer paths
 Larger quantum of extra
space provision
 More disposables used
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 Single Product Facility
 One/two batch sizes,
defined process
 Sizing, flows
straightforward
 Utilities sized to batch
volumes & process
schedules
 Defined operating range
 Fixed equipment preferred
over disposables
 No additional space
provisions required.
 Regulatory requirements
 Which regulator will approve the facility? What do they
require?
 Are there any key flags to look for?
 Talk to the regulators & get a feel of their opinion prior to
basic/detail design.

 EU needs Class A in B for inoculum prep.

 India does not specify viral segregation.
 PICS & others like Indonesia require separate PAL MAL
 USFDA open to considering V+, V- process steps in the
same room.
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 Emerging Trends in Facility
Design
 Disposable/ Single use systems

 Use of “Controlled Non Classified (CNC)” areas

 Multi-product facilities with parallel operations

 Modular Plants & Superskids

 “Visual Factories” and “Open Space” concepts

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 Single Use Products: Influence
on Facility Design
 Reducing requirement of
cleaning spaces –
SIP/CIP/SOP/COP, Staging,
tank movement …
 Reduced Size of Utilities and
Piping – both Central Utilities
and within a process room
 Easily validatable closed
systems allow use of lower air
classification
 Rapid deployment – less
planning due to low cost of
capital
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 Use of CNC Areas
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 Multi-product facilities with
parallel operations
 Historically:
Multiproduct Operation = Campaign mode
 Newer technologies for closed operations and risk
based approach
 Manufacturers pushing for simultaneous multi-product
operations
 Regulators more open to concept – Ok if segregation
and cross contamination issues are addressed
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 Modular Plants and
Superskids
 Superskids: Reduce sitework, shrink
timelines, offsite Qualification
 Modular plants: Designed, constructed,
integrated offsite
 Reduce sitework
 Condense Construction Timelines
 Pre-tested & integrated- no last minute
surprises
 Higher Cost, Suited for midsized plants,
infrastructural constraints
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 Workplaces not Factories
 To provide better working environment
 Moving away from windowsless artificially lighted rooms
 Contract manufacturers- key drivers: To attract potential
customers
 Influence Design – room placements, adjacencies
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 Designing a Facility
 Start with defining the process, lay down operational
requirements

 Build the facility around the process- add functional areas

around the process

 Flexibility comes at a price

 Design only for more expected variables Ex. 85% process

coverage of LAMP
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 The Facility Design Process

 Facility URS
 Conceptual Design (3-4 months) Basic layouts, site plan, building
sizing, utilities-basic plan and sizing, line diagrams, equipment
lists, overall philosophies & budget cost (+ 25%)
 Basic Design (3-4 months)- Room sizing, utility sizing, detailed
layout, equipment URSs, P & IDs and cost (+ 10%)
 Detailed Design (8-12 months): Full/detailed designing of all
elements. 1000s of drawings, 2D and 3 D designing
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 If you are lucky….

You will end up making THAT product, for

which you designed the facility!
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